Effect of calcium antagonists on aortae isolated from normotensive and hypertensive rats: relaxation and calcium influx blockade.
Verapamil and diltiazem were equally potent (ie, similar EC50s) in relaxing potassium-contracted aortas of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. The mechanical EC50s produced approximately 50% calcium influx blockade, suggesting a causal link between relaxation and calcium influx blockade. Nitrendipine was about 250 times more potent in relaxing aortic smooth muscle in SHR than in WKY rats (EC50s in -log [M] were 14.10 +/- 0.30 and 11.70 +/- 0.54, respectively). This difference was not affected by endothelial denudation, and was present when nitrendipine was used by preincubation rather than during established potassium chloride contractions. In spite of the different relaxant potency of nitrendipine in SHR and WKY rats, both strains showed similar EC50s for calcium influx blockade for this compound (9.21 +/- 0.36 in SHR and 8.75 +/- 0.26 in WKY). The dissociation between aortic smooth muscle relaxation and calcium influx blockade after nitrendipine was more pronounced in the SHR strain. This suggests that mechanisms other than or in addition to calcium influx blockade play a role in the relaxation of potassium-contracted vascular smooth muscle with dihydropyridine compounds, but not with other calcium antagonists.
Cattaneo
E A
EA
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Medicas, La Plata, Argentina.
Rinaldi
G J
GJ
Cingolani
H E
HE
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D006973:Hypertension / Q000188:drug therapy; D066298:In Vitro Techniques; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014700:Verapamil / Q000494:pharmacology*
D009568:Nitrendipine; D014700:Verapamil; D004110:Diltiazem; D002118:Calcium