QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.061150v1 309/2/684    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Okajima, K. Articles by Isobe, H. Search for Related Content PubMed PubMed Citation Articles by Okajima, K. Articles by Isobe, H.

CARDIOVASCULAR

Activation of Capsaicin-Sensitive Sensory Neurons by Carvedilol, a Nonselective -Blocker, in Spontaneous Hypertensive Rats

Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

We performed a study in spontaneous hypertensive rats (SHR) to determine whether carvedilol, a nonselective -adrenoceptor antagonist, activates capsaicin-sensitive sensory neurons (CSSNs), thereby promoting the release of calcitonin gene-related peptide (CGRP), a neuropeptide with an important role in maintenance of cardiovascular homeostasis. Carvedilol given intravenously at a dose of 0.3 mg/kg transiently decreased the mean arterial blood pressure (MABP) and increased renal tissue blood flow with increases in CGRP levels in plasma and kidney. These effects induced by carvedilol were not seen in animals pretreated with capsazepine, an antagonist of capsaicin. Although 1.0 mg/kg cavedilol markedly decreased MABP, it neither increased renal tissue blood flow nor CGRP levels in plasma and kidney. Prazosin, a selective ₁-adrenoceptor antagonist, and bisoprolol, a selective ₁-adrenoceptor antagonist, decreased MABP with capsazepine, showing no antagonistic action in either cases, and these agents increased neither renal tissue blood flow nor levels of CGRP in plasma and kidney. Both ICI 118,551 [(±)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol], a selective ₂-adrenoceptor antagonist, at a dose of 0.25 mg/kg and capsaicin mimicked effects induced by 0.3 mg/kg carvedilol. Administration of 1.0 mg/kg ICI 118,551 produced effects similar to those induced by 1.0 mg/kg carvedilol. These observations strongly suggested that the low dose of carvedilol might activate CSSNs in SHR to increase the release of CGRP, thereby decreasing blood pressure with an increase in renal tissue blood flow. The effects induced by carvedilol seemed to be mediated by its ₂-adrenoceptor blockade activity.

Address correspondence to: Dr. Kenji Okajima, Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo, 1-1-1 Kumamoto 860-0811, Japan. E-mail: whynot{at}kaiju.medic.kumamoto-u.ac.jp

This article has been cited by other articles:

				M. Bhatia, L. Zhi, H. Zhang, S.-W. Ng, and P. K. Moore Role of substance P in hydrogen sulfide-induced pulmonary inflammation in mice Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L896 - L904. [Abstract] [Full Text] [PDF]