Comparison of Inhibitory Effects of Calcium Channel Blockers and That of a Calmodulin Antagonist in Strips of Mesenteric Arteries from Spontaneously Hypertensive and Normotensive Rats

Abstract

Abstract-Effectsof calcium channel blockers and of calmodulin antagonist on the contractile responses to norepinephrine (NE) were compared between strips of mesenteric arteries from 6 and 14-week-old spontaneously hypertensive rats (SHR) and age-matched, normotensive Wistar-Kyoto rats (WKY). The ratio of the maximum contraction developed by NE to that by 60 mM KCI was significantly increased in strips from 14-week-old SHR. Niludipine, verapamil and diltiazem antagonized the maximum NE contraction to a greater extent in strips from 14-week old SHR than in those from the WKY. However, the antagonism by niludipine of the KCI or caffeine-induced contraction was not significantly different between the strips from 14-week-old SH R and those from WKY. In strips from 6-week-old rats, there was no difference in the antagonism by niludipine of the maximum NE con traction.On the other hand, the effect of W-7 on the maximum N E contraction was not significantly different between the strips from 14-week-old SHR and those from WKY. Schild plot analyses demonstrated that a,-adrenoceptors were the same for the strips from SHR and WKY. These results suggest that the enhanced maximum NE contraction in the mesenteric artery from 14-week-old SHR reflects the increased transmembrane influx of calcium, and the activity of calmodulin seems to be the same for the two strains.

Impaired function of alpha‐2 adrenoceptors in smooth muscle of mesenteric arteries from spontaneously hypertensive rats

“…A less negative membrane potential has also been observed in other vascular smooth muscle from SHR such as the caudal artery (Hermsmeyer et al, 1982). This may account for the enhancement of vascular responsiveness observed by several authors (Asano et al, 1988). Also, the membrane potential of mesenteric arteries from SHR was not aected by apamin as observed in normotensive animals suggesting, again, that the activity of apamin-sensitive K + channels is reduced in SHR mesenteric arteries.…”

Caffeine-Induced Contraction in Arteries from Stroke-Prone Spontaneously Hypertensive Rats

“…Changes in Ca sensitivity of the contractile protein of smooth muscle of SHRSP mesenteric artery would not be involved as has been reported in chemi cally skinned preaparations [25]. Although changes in myoplasmic regulatory compo nents which would be lost by the skinning procedure, cannot be excluded, at least the activity of calmodulin has been reported to be the same in WKY and SHR vascular smooth muscle [26], The release of Ca by caffeine has been reported in Ca-efflux as well as in Ca-indicator experiments [15,16,19,20,[27][28][29], and there is good correlation between the caf feine-induced increase in intracellular Ca and contraction amplitude [20]. In addition, the results that procaine [18,30] or ryano dine [23] blocked the caffeine-induced con traction in Ca-free solution also support the concept that caffeine releases Ca from sarco plasmic reticulum in smooth muscle of the mesenteric arteries, both from SHRSP and WKY.…”