Budzyn, K., Ravi, R.M., Miller, A.A. and Sobey, C.G. (2009) Mechanisms of augmented vasoconstriction induced by 5-hydroxytryptamine in aortic rings from spontaneously hypertensive rats. British Journal of Pharmacology, 155(2), pp. 210-216. (doi: 10.1038/bjp.2008.247) (PMID:18552867) (PMCID:PMC2538692)
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Abstract
Background and purpose: To test whether development of enhanced vasoconstriction to 5-hydroxytryptamine (5-HT; serotonin) in SHR was temporally related to hypertension, elevated vascular superoxide (O2−) levels, decreased NO bioavailability, or increased contractile effects of cyclooxygenase or rho-kinase and/or PKC. Experimental approach: We examined systolic blood pressure (SBP), vascular O2−, and 5-HT-induced contractile responses of aortic segments from 4- and 8-week-old WKY and SHR. Key results: SBP was 35% higher in SHR than WKY at 4 weeks and 60% higher at 8 weeks. Contractile responses to 5-HT were similar in WKY and SHR at 4 weeks, but were markedly augmented in SHR at 8 weeks. The NO synthase inhibitor, L-NAME, enhanced contractile responses to 5-HT markedly in both strains at 4 weeks and in WKY at 8 weeks, but only very modestly in SHR at 8 weeks. These functional differences were associated with higher O2− levels in SHR versus WKY at 8 weeks, but not at 4 weeks. The rho-kinase inhibitor, Y-27632, and the PKC inhibitor, Ro 31-8220, each only modestly attenuated contractions in WKY and SHR in each age group, and their effects in each strain were more pronounced at 8 weeks. The cyclooxygenase inhibitor, indomethacin, had no effect on contractile responses. Conclusions and implications: Development of augmented vascular contractile responses to 5-HT in SHR is preceded by hypertension. It is associated with increased vascular O2− levels and reduced modulatory effects of NO, and is unlikely to be due to enhanced activity of rho-kinase, PKC or cyclooxygenase.
| Item Type: | Articles |
|---|---|
| Additional Information: | This study was supported by funds from Project grants fromthe National Health and Medical Research Council ofAustralia (NHMRC ID 208969, 350477). KB was supportedby a Melbourne University Research Scholarship and iscurrently supported by a CJ Martin Overseas TrainingFellowship from the NHMRC. AAM is a Postdoctoral Fellowof the Foundation for High Blood Pressure Research,Australia. CGS is a Senior Research Fellow of the NHMRC. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Miller, Dr Alyson |
| Authors: | Budzyn, K., Ravi, R.M., Miller, A.A., and Sobey, C.G. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | British Journal of Pharmacology |
| Publisher: | Wiley |
| ISSN: | 0007-1188 |
| ISSN (Online): | 1476-5381 |
| Published Online: | 29 January 2009 |
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