GO:0003044 regulation of systemic arterial blood pressure mediated by a chemical signal: Hormonal Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0003044 describes the biological process by which biochemical signals, including hormones, autocrine and paracrine factors, regulate systemic arterial blood pressure [1,2,3].
• Angiotensin II, vasopressin, nitric oxide, and calcitonin gene-related peptide are central chemical mediators of this process [2,3,5,6].
• Dysregulation of this process contributes to hypertension, portal hypertensive syndrome, and systemic inflammatory responses [1,2,4].
• Key signaling pathways include VEGFR-2, angiotensin II, mTOR/MEK1/ERK1/2/NF-kB, and NMDA receptor signaling [1,2,4,7].
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal dissection of genes controlling blood pressure regulation [1,2,4].
• EDITGENE provides end-to-end CRISPR cell model and library screening services to study GO:0003044-related genes.
Description
Regulation of systemic arterial blood pressure mediated by a chemical signal (GO:0003044) is a biological process that encompasses the control of arterial blood pressure through biochemical signaling molecules, including hormones, autocrine factors, and paracrine factors [1,2,3]. This process is fundamental to cardiovascular homeostasis and is a major research focus because its dysregulation underlies hypertension, portal hypertensive syndrome, and other cardiovascular pathologies [1,2]. The QuickGO definition specifies that this regulation is mediated by biochemical signaling, distinguishing it from neural or mechanical control mechanisms [1,3]. Understanding the molecular players and signaling cascades involved is essential for developing targeted therapeutic strategies [2,4]. Experimental evidence from animal models demonstrates that angiotensin II signaling augmentation causes aortic dysfunction and systemic hypertension, while high salt intake can reduce vascular nitric oxide even in the absence of hypertension. These findings highlight the complexity and clinical relevance of chemical signal-mediated blood pressure regulation.
regulation of systemic arterial blood pressure mediated by a chemical signal At A Glance
| GO ID | GO:0003044 |
|---|---|
| GO term | regulation of systemic arterial blood pressure mediated by a chemical signal |
| Ontology | biological_process |
| Synonym | blood pressure regulation mediated by a chemical signal |
| Major function | Biochemical control of systemic arterial blood pressure via hormones, autocrine and paracrine signals |
| Key mediators | Angiotensin II, vasopressin, nitric oxide, CGRP, VEGFR-2 signaling |
| Associated diseases | Hypertension, portal hypertensive syndrome, systemic inflammatory response |
| Research models | Rodent models, CRISPR knockout/knock-in cell models, pharmacological inhibition |
What Is GO:0003044?
GO:0003044 is defined as the regulation of blood pressure mediated by biochemical signaling, including hormonal, autocrine, or paracrine signals. In other words, it is the process by which chemical messengers such as angiotensin II, vasopressin, nitric oxide, and calcitonin gene-related peptide modulate systemic arterial blood pressure [2,3,5,6]. This term captures the biochemical control layer of blood pressure homeostasis, excluding purely neural or mechanical regulation.
Why Is regulation of systemic arterial blood pressure mediated by a chemical signal Important in Cell Biology?
GO:0003044 is critically important because chemical signal-mediated blood pressure regulation is a central determinant of cardiovascular health, and its dysfunction is directly linked to hypertension, portal hypertensive syndrome, and systemic inflammatory conditions [1,2,4]. The process integrates hormonal, autocrine, and paracrine signals that control vascular tone, cardiac output, and fluid balance [2,3,6]. Experimental studies show that angiotensin II signaling augmentation causes systemic hypertension and aortic dysfunction, while VEGFR-2 inhibition ameliorates portal hypertensive syndrome in cirrhotic rats. Additionally, mTOR inhibition protects against systemic inflammatory response and oxidative stress, and vasopressin V1a receptors in the carotid body contribute to breathing control. These findings underscore the therapeutic potential of targeting this process.
• Hypertension is a leading global health burden, and chemical signal-mediated blood pressure regulation is a core mechanism in its pathogenesis.
• Angiotensin II signaling augmentation directly causes aortic dysfunction and systemic hypertension in animal models.
• VEGFR-2 signaling inhibition ameliorates portal hypertensive syndrome in cirrhotic rats.
• High salt intake reduces vascular nitric oxide, linking dietary factors to chemical blood pressure regulation.
• mTOR inhibition protects against systemic inflammatory response and oxidative/nitrosative stress.
• Calcitonin gene-related peptide and RAMP1 regulate colonic vascular conductance.
• Vasopressin V1a receptors in the carotid body contribute to breathing control and blood pressure regulation.
• NMDA receptors in the median preoptic nucleus mediate hemodynamic responses to stress.
• CRISPR-based models enable causal testing of candidate genes in this process [1,2,4].
• Therapeutic targeting of these pathways may yield new treatments for cardiovascular and inflammatory diseases [1,2,4].
What Happens During regulation of systemic arterial blood pressure mediated by a chemical signal?
Hormonal signaling initiation
In simple terms: Hormones like angiotensin II are released into the blood and trigger blood pressure changes.
The process begins with the release of hormonal signals such as angiotensin II, which acts on vascular smooth muscle and other tissues to increase blood pressure. In rats, arsenic exposure augments angiotensin II signaling, causing aortic dysfunction and systemic hypertension. This demonstrates that hormonal signals are primary initiators of GO:0003044. Additionally, vasopressin V1a receptors in the carotid body contribute to the control of breathing and cardiovascular function, further illustrating hormonal initiation of blood pressure regulation.
Autocrine and paracrine modulation
In simple terms: Local chemical signals released by cells affect nearby cells to fine-tune blood pressure.
Autocrine and paracrine signals, including nitric oxide and calcitonin gene-related peptide (CGRP), modulate vascular tone locally [3,5]. High salt intake reduces vascular nitric oxide bioavailability, impairing endothelial function even without hypertension. Daikenchuto increases colonic vascular conductance via CGRP and receptor-activity modifying protein 1 (RAMP1), showing that paracrine signals regulate regional blood flow and systemic pressure. These local signals integrate with hormonal signals to maintain blood pressure homeostasis.
Receptor-mediated signal transduction
In simple terms: Chemical signals bind to receptors on cells, triggering internal signaling cascades.
Chemical signals bind to specific receptors, such as VEGFR-2, angiotensin receptors, vasopressin V1a receptors, and NMDA receptors, initiating intracellular signaling [1,2,6,7]. Cediranib, a VEGFR-2 inhibitor, ameliorates portal hypertensive syndrome in cirrhotic rats, demonstrating the role of VEGFR-2 signaling in this process. Angiotensin and NMDA receptors in the median preoptic nucleus mediate hemodynamic response patterns to stress. These receptor-mediated events translate chemical signals into physiological changes in blood pressure.
Downstream effector pathways
In simple terms: Signals activate pathways like mTOR and NF-kB that change blood vessel tone and inflammation.
Downstream effectors include the mTOR/MEK1/ERK1/2/IKKbeta/IkappaB-alpha/NF-kappaB signaling pathway, which contributes to systemic inflammatory response and oxidative/nitrosative stress. mTOR inhibition protects against zymosan-induced systemic inflammatory response, indicating that this pathway modulates chemical signal-mediated blood pressure regulation. These effector pathways alter vascular smooth muscle contraction, endothelial function, and inflammatory status, ultimately regulating systemic arterial blood pressure.
Integration and feedback
In simple terms: The body integrates multiple chemical signals to keep blood pressure stable.
The process integrates hormonal, autocrine, and paracrine signals through complex feedback loops involving the vasculature, kidney, and central nervous system [2,6,7]. For example, vasopressin V1a receptors in the carotid body contribute to breathing control, which indirectly affects blood pressure. NMDA receptors in the median preoptic nucleus mediate hemodynamic responses to stress, linking neural and chemical regulation. This integration ensures that blood pressure is maintained within a physiological range despite varying demands.
Key Genes Involved in GO:0003044 regulation of systemic arterial blood pressure mediated by a chemical signal
The following genes and proteins are experimentally validated mediators of chemical signal-mediated systemic arterial blood pressure regulation.
| Gene | Major Role | Research Relevance |
|---|---|---|
| AGTR1 | Angiotensin II receptor type 1; mediates vasoconstriction and hypertension | Target for hypertension and aortic dysfunction studies |
| VEGFR2 | Vascular endothelial growth factor receptor 2; regulates vascular permeability and portal hypertension | Inhibited by cediranib to ameliorate portal hypertensive syndrome |
| NOS3 | Endothelial nitric oxide synthase; produces nitric oxide for vasodilation | Reduced by high salt intake, impairing endothelial function |
| CALCA | Calcitonin gene-related peptide; regulates vascular conductance | Mediates Daikenchuto-induced colonic vascular conductance |
| RAMP1 | Receptor-activity modifying protein 1; modulates CGRP receptor function | Involved in colonic vascular conductance regulation |
| AVPR1A | Vasopressin V1a receptor; controls breathing and cardiovascular function | Present in carotid body, contributes to blood pressure control |
| GRIN1 | NMDA receptor subunit 1; mediates hemodynamic stress responses | In median preoptic nucleus, mediates stress-induced hemodynamic patterns |
| GRIN2A | NMDA receptor subunit 2A; involved in central blood pressure regulation | Part of NMDA receptor complex in median preoptic nucleus |
| MTOR | mTOR kinase; regulates inflammatory and oxidative stress pathways | Inhibition protects against systemic inflammatory response |
| MAP2K1 | MEK1 kinase; part of mTOR/MEK1/ERK1/2 pathway | Contributes to oxidative/nitrosative stress signaling |
| MAPK3 | ERK1 kinase; downstream of MEK1 in inflammatory signaling | Involved in mTOR-dependent inflammatory response |
| IKBKB | IKKbeta kinase; activates NF-kappaB | Part of mTOR/MEK1/ERK1/2/IKKbeta/IkappaB-alpha/NF-kappaB pathway |
| NFKB1 | NF-kappaB subunit; regulates inflammatory gene expression | Mediates oxidative/nitrosative stress in systemic inflammation |
| VEGFA | VEGF ligand; activates VEGFR-2 signaling | Upstream of VEGFR-2 in portal hypertension |
| ACE | Angiotensin-converting enzyme; produces angiotensin II | Central to angiotensin II-mediated hypertension |
| REN | Renin; rate-limiting enzyme in angiotensin II production | Upstream regulator of angiotensin II signaling |
| AGT | Angiotensinogen; precursor of angiotensin peptides | Substrate for renin and angiotensin II generation |
How Is regulation of systemic arterial blood pressure mediated by a chemical signal Regulated?
The process of chemical signal-mediated blood pressure regulation is itself regulated by multiple mechanisms. The mTOR pathway modulates systemic inflammatory response and oxidative/nitrosative stress through the mTOR/MEK1/ERK1/2/IKKbeta/IkappaB-alpha/NF-kappaB signaling axis. Inhibition of mTOR protects against zymosan-induced systemic inflammatory response, indicating that mTOR is a key regulator of this process. Additionally, VEGFR-2 signaling regulates portal hypertension, and its inhibition by cediranib ameliorates portal hypertensive syndrome in cirrhotic rats. Angiotensin II signaling is augmented by arsenic exposure, leading to aortic dysfunction and systemic hypertension. High salt intake reduces vascular nitric oxide, demonstrating dietary regulation of this process. These findings show that GO:0003044 is subject to regulation by pharmacological, dietary, and inflammatory inputs.
regulation of systemic arterial blood pressure mediated by a chemical signal and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| AGTR1 | Hypertension, aortic dysfunction | CRISPR knockout rat or mouse model |
| VEGFR2 | Portal hypertensive syndrome | Cediranib-treated cirrhotic rat model |
| NOS3 | Endothelial dysfunction, salt-sensitive hypertension | High salt diet rat model |
| MTOR | Systemic inflammatory response | Zymosan-induced inflammation model |
| AVPR1A | Breathing and cardiovascular control | Carotid body-specific knockout model |
Hypertension and cardiovascular dysfunction
Dysregulation of chemical signal-mediated blood pressure regulation is a primary cause of hypertension. Arsenic exposure augments angiotensin II signaling, causing aortic dysfunction and systemic hypertension in rats. High salt intake reduces vascular nitric oxide bioavailability, impairing endothelial function and contributing to blood pressure elevation. These studies demonstrate that environmental and dietary factors can disrupt GO:0003044, leading to cardiovascular disease.
Portal hypertensive syndrome
Portal hypertensive syndrome is a complication of cirrhosis characterized by elevated blood pressure in the portal venous system. Cediranib, a VEGFR-2 inhibitor, ameliorates portal hypertensive syndrome in cirrhotic rats by inhibiting VEGFR-2 signaling. This finding links GO:0003044 to liver disease and identifies VEGFR-2 as a therapeutic target for portal hypertension.
Systemic inflammatory response
Systemic inflammatory response and oxidative/nitrosative stress are closely linked to blood pressure dysregulation. mTOR inhibition protects against zymosan-induced systemic inflammatory response through the mTOR/MEK1/ERK1/2/IKKbeta/IkappaB-alpha/NF-kappaB pathway. This suggests that inflammatory signaling contributes to the pathogenesis of blood pressure disorders and that targeting this pathway may be beneficial.
Stress-induced hemodynamic changes
Stress can trigger hemodynamic responses through chemical signals in the brain. Angiotensin and NMDA receptors in the median preoptic nucleus mediate hemodynamic response patterns to stress. Vasopressin V1a receptors in the carotid body also contribute to the control of breathing and cardiovascular function. These findings link GO:0003044 to neuroendocrine regulation of blood pressure under stress.
From regulation of systemic arterial blood pressure mediated by a chemical signal-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does angiotensin II receptor knockout prevent arsenic-induced hypertension? | AGTR1 knockout rat |
| Does VEGFR-2 inhibition reduce portal hypertension? | Cediranib-treated cirrhotic rat |
| Does NOS3 overexpression restore endothelial function under high salt? | NOS3 overexpression mouse |
| Does mTOR point mutation alter inflammatory response? | MTOR knock-in mouse |
| Does CGRP receptor knock-in enhance vascular conductance? | RAMP1 knock-in mouse |
| Does vasopressin V1a receptor knockout affect breathing control? | AVPR1A knockout rat |
How to Study the regulation of systemic arterial blood pressure mediated by a chemical signal Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Telemetry | Systemic arterial blood pressure | Long-term blood pressure monitoring in rodents |
| Tail-cuff plethysmography | Systolic blood pressure | Non-invasive blood pressure measurement |
| Western blot | Protein expression and phosphorylation | Signaling pathway analysis |
| Immunohistochemistry | Protein localization in tissues | Carotid body V1a receptor detection |
| CRISPR knockout | Gene function loss | Causal testing of candidate genes [1,2] |
| CRISPR knock-in | Mutant protein expression | Point mutation modeling |
| RNA-seq | Transcriptomic changes | Global gene expression profiling |
| Proteomics | Protein abundance and modifications | Pathway discovery |
Hemodynamic measurements
Direct measurement of systemic arterial blood pressure using telemetry or tail-cuff plethysmography is essential to quantify the output of GO:0003044. Studies in rats have used these methods to demonstrate that arsenic-induced angiotensin II signaling augmentation causes systemic hypertension and that high salt intake reduces vascular nitric oxide without hypertension. These techniques provide functional readouts of chemical signal-mediated blood pressure regulation.
Molecular signaling assays
Western blotting, immunoprecipitation, and kinase activity assays are used to dissect signaling pathways. For example, the mTOR/MEK1/ERK1/2/IKKbeta/IkappaB-alpha/NF-kappaB pathway was characterized using these methods in the context of systemic inflammatory response. VEGFR-2 signaling inhibition by cediranib was validated using molecular assays in cirrhotic rats. These techniques identify the molecular mechanisms underlying GO:0003044.
Genetic manipulation in animal models
CRISPR/Cas9-mediated knockout, knock-in, and point mutation models enable causal testing of candidate genes. For instance, knockout of angiotensin receptors or VEGFR-2 can determine their necessity in blood pressure regulation [1,2]. Overexpression of NOS3 can test sufficiency in restoring endothelial function. These genetic approaches are powerful for establishing causality in GO:0003044.
Pharmacological intervention
Pharmacological inhibitors and agonists are used to probe the role of specific signaling molecules. Cediranib, a VEGFR-2 inhibitor, ameliorates portal hypertensive syndrome. mTOR inhibitors protect against systemic inflammatory response. These pharmacological tools complement genetic approaches and provide translational insights into GO:0003044.
How CRISPR Can Be Used to Study GO:0003044 regulation of systemic arterial blood pressure mediated by a chemical signal
Knockout
CRISPR knockout models are used to eliminate candidate genes and assess their necessity in chemical signal-mediated blood pressure regulation. For example, knocking out AGTR1 or VEGFR2 can determine whether these receptors are required for angiotensin II-induced hypertension or portal hypertensive syndrome [1,2]. Knockout of MTOR or its downstream effectors can test their role in systemic inflammatory response. These models provide definitive loss-of-function evidence.
Point Mutation
CRISPR point mutation models introduce specific amino acid changes to dissect protein function. For instance, mutating phosphorylation sites in MEK1 or ERK1 can test their role in the mTOR/MEK1/ERK1/2 pathway. Point mutations in AVPR1A can reveal residues critical for vasopressin V1a receptor function in the carotid body. These models are valuable for understanding molecular mechanisms.
Knock-in
CRISPR knock-in models insert reporter tags or human disease variants to study gene function and localization. Tagged knock-in of RAMP1 or CALCA can track CGRP receptor dynamics in vascular conductance. Knock-in of human NOS3 variants can model endothelial dysfunction. These models enable precise tracking and functional analysis.
Overexpression
CRISPR overexpression models increase gene dosage to test sufficiency. Overexpressing NOS3 can restore nitric oxide production under high salt conditions. Overexpressing VEGFA can enhance VEGFR-2 signaling and exacerbate portal hypertension. These models complement knockout studies by demonstrating gain-of-function effects.
How EDITGENE Supports regulation of systemic arterial blood pressure mediated by a chemical signal Research
Researchers studying regulation of systemic arterial blood pressure mediated by a chemical signal-related genes often need to determine whether a candidate gene is causally involved in the process or merely correlated with it. EDITGENE provides a comprehensive suite of CRISPR-based services to enable this causal dissection, from knockout and point mutation to knock-in and overexpression models, as well as library screening and bioinformatics support.
Contact EDITGENE today to design your custom CRISPR model for regulation of systemic arterial blood pressure mediated by a chemical signal research.
Frequently Asked Questions About regulation of systemic arterial blood pressure mediated by a chemical signal
What is GO:0003044?
GO:0003044 is the Gene Ontology term for regulation of systemic arterial blood pressure mediated by a chemical signal, encompassing hormonal, autocrine, and paracrine control of blood pressure [1,2,3].
What genes are involved in regulation of systemic arterial blood pressure mediated by a chemical signal?
Key genes include AGTR1, VEGFR2, NOS3, CALCA, RAMP1, AVPR1A, GRIN1, MTOR, and MAP2K1, among others [1,2,3,4,5,6,7].
How does angiotensin II regulate blood pressure?
Angiotensin II binds to AGTR1, causing vasoconstriction and hypertension; arsenic exposure augments this signaling, leading to aortic dysfunction.
What is the role of VEGFR-2 in portal hypertension?
VEGFR-2 signaling contributes to portal hypertensive syndrome; its inhibition by cediranib ameliorates the condition in cirrhotic rats.
How does high salt intake affect blood pressure regulation?
High salt intake reduces vascular nitric oxide bioavailability, impairing endothelial function even without hypertension.
What is the role of mTOR in blood pressure regulation?
mTOR modulates systemic inflammatory response and oxidative stress through the mTOR/MEK1/ERK1/2/NF-kappaB pathway.
How does vasopressin V1a receptor contribute to blood pressure control?
Vasopressin V1a receptors in the carotid body contribute to the control of breathing and cardiovascular function.
What is the role of CGRP in vascular conductance?
Calcitonin gene-related peptide (CGRP) and RAMP1 mediate colonic vascular conductance, affecting regional blood flow.
How do NMDA receptors mediate stress-induced hemodynamic responses?
Angiotensin and NMDA receptors in the median preoptic nucleus mediate hemodynamic response patterns to stress.
What CRISPR models are available to study GO:0003044?
EDITGENE offers knockout, point mutation, knock-in, and overexpression models for genes such as AGTR1, VEGFR2, NOS3, and MTOR [1,2,3,4].
Conclusion
GO:0003044, regulation of systemic arterial blood pressure mediated by a chemical signal, is a vital biological process integrating hormonal, autocrine, and paracrine signals to control blood pressure. Experimental evidence from rodent models has identified key mediators including angiotensin II, VEGFR-2, nitric oxide, CGRP, vasopressin, and mTOR signaling [1,2,3,4,5,6,7]. Dysregulation of this process contributes to hypertension, portal hypertensive syndrome, and systemic inflammatory response. CRISPR-based models are powerful tools for dissecting the causal roles of individual genes in this process. EDITGENE provides comprehensive CRISPR services to support research on GO:0003044 and related cardiovascular diseases.
References
- 1. Fan Q et al.. 2024. Cediranib ameliorates portal hypertensive syndrome via inhibition of VEGFR-2 signaling in cirrhotic rats.. Eur J Pharmacol 964:176278 PMID: 38158116
- 2. Waghe P et al.. 2015. Arsenic causes aortic dysfunction and systemic hypertension in rats: Augmentation of angiotensin II signaling.. Chem Biol Interact 237:104-14 PMID: 26079204
- 3. Boegehold MA. 2013. The effect of high salt intake on endothelial function: reduced vascular nitric oxide in the absence of hypertension.. J Vasc Res 50(6):458-67 PMID: 24192502
- 4. Sahan-Firat S et al.. 2018. Protection by mTOR Inhibition on Zymosan-Induced Systemic Inflammatory Response and Oxidative/Nitrosative Stress: Contribution of mTOR/MEK1/ERK1/2/IKKβ/IκB-α/NF-κB Signalling Pathway.. Inflammation 41(1):276-298 PMID: 29110153
- 5. Kono T et al.. 2008. Colonic vascular conductance increased by Daikenchuto via calcitonin gene-related peptide and receptor-activity modifying protein 1.. J Surg Res 150(1):78-84 PMID: 18561951
- 6. Żera T et al.. 2018. Vasopressin V1a receptors are present in the carotid body and contribute to the control of breathing in male Sprague-Dawley rats.. Peptides 102:68-74 PMID: 29524562
- 7. Schwartz JA et al.. 2008. Angiotensin and NMDA receptors in the median preoptic nucleus mediate hemodynamic response patterns to stress.. Am J Physiol Regul Integr Comp Physiol 295(1):R155-65 PMID: 18434439
