<Originals>Pharmacological investigation of peptide-induced vasorelaxation in the isolated intrarenal arteries of stroke-prone spontaneously hypertensive rats
スポンサーリンク
概要
- 論文の詳細を見る
This study was designed to investigate the effects of various vasodilator peptides in the isolated intrarenal arteries (IRA) of strokeprone spontaneously hypertensive rats (SHRSP). In noradrenaline-precontracted IRA of 6-7 month old rats, calcitonin gene-related peptide (CGRP) provoked significantly greater endothelium-independent relaxation in SHRSP than in Wistar-Kyoto rats (WKY) with pD_2 estimates of 8.85 and 8.13 respectively (p<0.01). This relaxation was reversibly inhibited by human CGRP_<8-37> (10^<-6>M), a CGRP_1 receptor antagonist. Amylin amide and adrenomedullin also produced greater relaxation in SHRSP than in WKY with pD_2 values of 7.59 and 7.4 for SHRSP and of 7.04 and 7.02 for WKY, respectively (p<0.01). No significant differences between SHRSP and WKY were observed in the endothelium-independent relaxation responses to atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), c-type natriuretic peptide, vasoactive intestinal peptide (VIP), and peptide histidine isoleucine. Bradykinin produced minor endothelium-dependent vasodilation similarly in the two strains. Substance P and neurokinin A did not relax the IRA at all. Furthermore, response to CGRP was also evaluated in younger SHRSP. It was found that reactivity to CGRP was still significantly greater in SHRSP aged 3 and 1.5 months than in age-matched WKY. In addition, a notable decline in the magnitude of CGRP-induced response was found in WKY as the age increased from 1.5 to 6-7 months, whereas in SHRSP no such age-related decrease was observed. Neither significant differences between the two strains nor significant age-dependent variations in either strain were found in relaxation responses to dibutyryl cyclic AMP, forskolin, and 3-isobutyl-1-methylxanthine. Incubation with glibenclamide (10^<-6>M) did not affect CGRP-induced relaxation in both SHRSP and WKY at all the ages used. In summary, the present results show that several peptides, such as CGRP, ANP, BNP, and VIP, are able to relax rat IRA remarkably, suggesting their possible role in modulating intrarenal vascular tone. In SHRSP, a significantly increased relaxation response to CGRP_1 receptor stimulation and lack of age-related reduction of this enhanced response are demonstrated. These changes found in SHRSP may not be a post-receptor event relating to second messengers like cyclic AMP, or to ATP-dependent potassium channels.
著者
関連論文
- Pharmacological investigation of peptide-induced vasorelaxation in the isolated intrarenal arteries of stroke-prone spontaneously hypertensive rats
- Responses to seven vasorelaxant neuropeptides in small renal arteries isolated from stroke prone spontaneously hypertensive rats
- Relaxant Effects of Calcitonin Gene-related Peptide on Isolated Small Renal Arteries in Stroke-Prone Spontaneously Hypertensive Rats.