Dissociation between calcium influx blockage and smooth muscle relaxation by nifedipine in spontaneously hypertensive rats.
Aortic smooth muscle isolated from spontaneously hypertensive rats (SHR) and normotensive, age-matched Wistar Kyoto rats (WKY) was precontracted by potassium chloride. The relaxant effect of nifedipine (NIF) was much more pronounced in SHR than in WKY, while the relaxation produced by nitroglycerin (NTG) was similar in both tissues. EC50s were (in - log [M]) NIF:SHR 13.1 +/- 0.4 and WKY 9.4 +/- 0.2 (p less than 0.05); NTG:SHR 7.35 +/- 0.3 and WKY 7.26 +/- 0.18 (NS). Aortas from SHR were less sensitive to the contractile effect of Ca2+ than their WKY controls (EC50 was 3.18 +/- 0.03 in WKY and 2.76 +/- 0.13 in SHR, p less than 0.05). The relaxant effect of NIF was dissociated from its effect on Ca2+ influx in SHR aortas. NIF 10(-10) M relaxed the muscle by 100% without producing Ca2+ influx blockage, and NIF 10(-9) and 10(-8) M induced Ca2+ influx blockage while the muscle continued in the relaxed state. Chemically skinned aortic fibers from SHR were less sensitive to the contractile effect of Ca2+ than their normotensive (NR) controls (pCa for EC50 was 5.91 +/- 0.05 in SHR and 6.20 +/- 0.03 in NR, p less than 0.05). NIF 10(-10) M depressed the contractile response to Ca2+ significantly more in SHR than in NR skinned fibers (pCa for EC50 for 5.62 +/- 0.09 in SHR and 6.07 +/- 0.07 in NR, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000627:therapeutic use*; D009994:Osmolar Concentration; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D002121:Calcium Channel Blockers; D009543:Nifedipine; D002118:Calcium