AUGMENTED CONTRIBUTIONS OF VOLTAGE-GATED CA2-ARTERIES( CHANNELS TO CONTRACTILE RESPONSES IN SPONTANEOUSLY HYPERTENSIVE RAT MESENTERIC)

The observation that organic Ca2+ channel blockers are more effective in lowering blood pressure and peripheral resistance in hypertensive c ompared to normotensive subjects suggests that there is a greater cont ribution from voltage-gated Ca2+ channels (Ca-L) to vascular force mai ntenance in hypertensive arteries. This study tests this hypothesis by comparing the effects of Bay k 8644 and nisoldipine on basal force de velopment, contractile responses to norepinephrine and serotonin, and Ca2+ currents (I-Ca) in mesenteric artery (MA) from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). MA rings were used to record isometric contractions at L-max. Single cells were isolated by collagenase plus elastase for measurement of Ca-L properties by patch -clamp methods. Contractile responses to Bay k 8644 were larger and mo re sensitive in SHR than WKY, and were larger in endothelium-denuded c ompared to intact rings. In SHR, the addition of 10 nmol/L Bay k 8644 increased contractile sensitivity to norepinephrine (NE) and serotonin (5HT), and increased maximum response to 5HT. In WKY, 10 nmol/L Bay k 8644 produced a small increase in 5HT sensitivity with no effect on m aximum response, and had no effect on NE responses. In the presence of 1 mu mol/L nisoldipine, the maximum response and the sensitivity to b oth NE and 5HT were decreased in both WKY and SHR with the inhibitory effects of nisoldipine being larger in SHR than WKY. Peak I-Ca was lar ger in SHR, and current-voltage curves were shifted toward more negati ve voltages compared to WKY. Bay k 8644 increased I-Ca in both WKY and SHR myocytes with no apparent difference in the magnitude of its effe ct when expressed as a percent of control I-Ca. These results suggest that Ca-L contribute significantly to tonic force maintenance as well as to agonist responses in MA from both WKY and SHR, but with a much l arger contribution in SHR. Differences in the sensitivity of Ca-L to B ay k 8644 were not responsible for the differences in contractile resp onses to this agonist. (C) 1997 American Journal of Hypertension, Ltd.