ABSTRACT-The relaxant effects of calcitonin gene-related peptide (CGRP) and other drugs were compared in basilar artery rings obtained from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). In addition, the relaxant effect of CGRP on basilar arteries from spon taneously hypertensive rats (SHR) was examined. Relaxation induced by CGRP was independent of the presence of endothelium, and it was markedly increased in SHRSP when compared to WKY. In contrast, acetylcholine-induced relaxation was endothelium-dependent and did not differ between the two groups. Enhanced CGRP-induced relaxation was also found in SHR when compared to WKY. However, the relaxant response was greater in SHRSP than in SHR. No significant differences were found in the relaxation induced by isoproterenol, forskolin, dibutyryl cyclic AMP, and 3-isobutyl-l methylxanthine in endothelium-rubbed arteries of WKY and SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the rat basilar artery, and that the enhanced CGRP induced relaxation found in SHRSP may not be associated with alterations of vasodilation mediated by cyclic AMP.Keywords: Calcitonin gene-related peptide (CGRP), Stroke-prone spontaneously hypertensive rats (SHRSP), Basilar artery, Vascular relaxation, Endothelium Calcitonin gene-related peptide (CGRP), translated from the calcitonin gene (1, 2), has been shown to be a potent vasodilator and to have a role in the regulation of both peripheral and cerebral vascular tone (3-5).It is well-documented that hypertension produces functional and morphological changes of the peripheral and cerebral vascular beds. Thus, an altered vascular response to CGRP would be expected in hypertensive animal models. It was recently demonstrated that the vasodilatory response to exogenously applied CGRP was significantly increased in spontaneously hyperten sive rats (SHR) when compared to Wistar-Kyoto rats (WKY), whereas no significant difference was found between rats with deoxycorticosterone-salt-induced hypertension and normotensive Wistar rats, in studies using isolated perfused mesenteric vascular beds (6, 7). However, there is little information available about the vascular response to CGRP in the cerebral arteries of hypertensive animals.In the present study, to determine whether cerebro vascular reactivity to CGRP was altered in hypertensive animal models, we examined the responses to CGRP and other drugs of isolated basilar arteries obtained from stroke-prone spontaneously hypertensive rats (SHRSP) (8). In addition, we examined the vascular re sponse of SHR basilar arteries to CGRP.
MATERIALS AND METHODS
AnimalsMale WKY, SHRSP, and SHR aged 6-7 months were used. Body weight was 356.2 ± 8.6 g (n = 20), 304.1 ± 5.8 g (n = 21), 373.8 ± 12.6 g (n = 4) for the WKY, SHRSP and SHR, respectively. Systolic blood pressure was measured by the standard tail cuff method; it was 144.3 ± 2.1 mmHg (n = 20), 225.5 ± 4.2 mmHg (n = 21), and 201.5 ± 8.5 mmHg (n = 4) for the WKY, SHRSP, and SHR groups, resp...
