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Urotensin II-induced hypotensive responses in Wistar–Kyoto (Wky) and spontaneously hypertensive (Shr) rats
| Content Provider | Semantic Scholar |
|---|---|
| Author | Gendron, Gabrielle Gobeil, Fernand Bélanger, Simon Gagnon, Sandra D'orléans-Juste, Pedro |
| Copyright Year | 2005 |
| Abstract | Human urotensin II (hU-II) is a potent vasoactive peptide which modulates some of the functions of the cardiovascular and other systems. The in vivo mechanism of action by which hU-II may influence blood pressure in developmental and pathological conditions, is poorly understood. Herein, the blood pressure effects of hU-II (0.1-10 nmol/kg) injected intravenously (i.v.) were studied on ketamine/xylazine anesthetized male WKY and SHR rats aged 4 and 8 weeks. hU-II elicited dose-dependent decreases in mean arterial pressure in both strains of animals. The hypotensive responses to hU-II were, however, significantly higher in SHR rats, independently of age. Four-week-old SHR rats (which are normotensive) were, however, less responsive than their hypertensive 8-week-old counterparts. A series of pharmacological inhibitors were used to identify putative endogenous (endothelial) factors that might account for the hU-II-mediated hypotension in 8-week-old SHR. These include the non-selective nitric oxide synthase inhibitor L-NAME (5 micromol/kg), the non-selective cyclooxygenase inhibitor meclofenamate (16 micromol/kg), the voltage-sensitive and ATP-sensitive K+-channel inhibitors, 4-aminopyridine (5 micromol/kg) and glybenclamide (10 micromol/kg), the cytochrome P450 CYP2C9 inhibitor sulfaphenazole (15 micromol/kg), the cytoskeletal fixation agent phalloidin (15 micromol/kg), the endothelin ETB receptor antagonist BQ-788(35 micromol/kg), the bradykinin B2 receptor antagonist HOE 140 (0.5 micromol/kg), the angiotensin AT2 antagonist PD 123319(10 micromol/kg) and the UT receptor antagonist urantide (10 micromol/kg). These agents were administered i.v. either at 2.5, 10 or 40 min prior hU-II injection (10 nmol/kg). Among these inhibitors, sulfaphenazole and phalloidin were able to reduce hU-II-induced hypotension. This suggests that the vasodepressor effect of hU-II is mediated by UT receptors and relies in part on the release of epoxide related products; increased microvascular permeability may also contribute to the blood pressure lowering effect of hU-II. Since urantide blocks the constrictor effects of hU-II on isolated aorta, but is inactive against the hypotensive action of hU-II in vivo, the results presented in this paper provide, for the first time, evidence for the existence of two different functional sites for hU-II. |
| Starting Page | 1468 |
| Ending Page | 1474 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.peptides.2005.03.012 |
| PubMed reference number | 16042987 |
| Journal | Medline |
| Volume Number | 26 |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0196978105001270 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0196978105001270?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | https://doi.org/10.1016/j.peptides.2005.03.012 |
| Journal | Peptides |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
