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Hypertension in mice with transgenic activation of the brain renin-angiotensin system is vasopressin dependent.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Littlejohn, Nicole K. Siel, Rick B. Ketsawatsomkron, Pimonrat Pelham, Christopher J. Pearson, Nicole A. Hilzendeger, Aline Mourão Buehrer, Beth A. Weidemann, Benjamin J. Li, Huiping Davis, Deborah R. Thompson, Anthony P. Liu, Xuebo Cassell, Martin D. Sigmund, Curt D. Grobe, Justin L. |
| Copyright Year | 2013 |
| Abstract | An indispensable role for the brain renin-angiotensin system (RAS) has been documented in most experimental animal models of hypertension. To identify the specific efferent pathway activated by the brain RAS that mediates hypertension, we examined the hypothesis that elevated arginine vasopressin (AVP) release is necessary for hypertension in a double-transgenic model of brain-specific RAS hyperactivity (the "sRA" mouse model). sRA mice experience elevated brain RAS activity due to human angiotensinogen expression plus neuron-specific human renin expression. Total daily loss of the 4-kDa AVP prosegment (copeptin) into urine was grossly elevated (≥8-fold). Immunohistochemical staining for AVP was increased in the supraoptic nucleus of sRA mice (~2-fold), but no quantitative difference in the paraventricular nucleus was observed. Chronic subcutaneous infusion of a nonselective AVP receptor antagonist conivaptan (YM-087, Vaprisol, 22 ng/h) or the V(2)-selective antagonist tolvaptan (OPC-41061, 22 ng/h) resulted in normalization of the baseline (~15 mmHg) hypertension in sRA mice. Abdominal aortas and second-order mesenteric arteries displayed AVP-specific desensitization, with minor or no changes in responses to phenylephrine and endothelin-1. Mesenteric arteries exhibited substantial reductions in V(1A) receptor mRNA, but no significant changes in V(2) receptor expression in kidney were observed. Chronic tolvaptan infusion also normalized the (5 mmol/l) hyponatremia of sRA mice. Together, these data support a major role for vasopressin in the hypertension of mice with brain-specific hyperactivity of the RAS and suggest a primary role of V(2) receptors. |
| Starting Page | 1705 |
| Ending Page | 1711 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| DOI | 10.1152/ajpregu.00082.2013 |
| PubMed reference number | 23535460 |
| Journal | Medline |
| Volume Number | 304 |
| Issue Number | 10 |
| Alternate Webpage(s) | http://ajpregu.physiology.org/content/ajpregu/304/10/R818.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1152/ajpregu.00082.2013 |
| Journal | American journal of physiology. Regulatory, integrative and comparative physiology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
