Effects of Bay K 8644 and nifedipine on femoral arteries of spontaneously hypertensive rats.
Vasoconstrictor effects of Bay K 8644 (an agonist known to increase Ca2+ influx through the voltage-dependent Ca2+ channels) on femoral arteries of 6 week old spontaneously hypertensive rats (SHR) were investigated, and data compared with findings in age-matched normotensive Wistar-Kyoto rats (WKY). The addition of Bay K 8644 (1 X 10(-10)-3 X 10(-7) M) elicited a dose-dependent contraction in SHR femoral artery in the absence of any contractile agent. Maximum contraction induced by this agonist was the same as the maximum induced by either K+-depolarization or alpha-adrenoceptor stimulation. Bay K 8644 was less effective in eliciting a contraction in the WKY femoral artery. Increased sensitivity to K+ was also observed in the SHR femoral artery. In contrast, contractions in response to alpha-adrenoceptor stimulation were the same in the SHR as those in the WKY. The addition of nifedipine, a Ca2+ channel antagonist, to an unstimulated preparation produced a dose-dependent relaxation in femoral arteries from SHR, but not from WKY. When the arteries were contracted with 60 mM K+, nifedipine produced similar relaxations in the SHR as those in the WKY, suggesting that the Ca2+ channels in the SHR femoral arteries are more activated than those in the WKY femoral arteries. Contractile responses to SHR femoral arteries to Bay K 8644 were antagonized competitively by nifedipine. Contractile responses to Ca2+ determined in K+-depolarized strips were also antagonized competitively by nifedipine. However, Schild plot analysis demonstrated a different pA2 value for nifedipine, suggesting that there may be a difference in the state of voltage-dependent Ca2+ channels in SHR femoral artery between the stimulation with Bay K 8644 and K+-depolarization.
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005263:Femoral Artery / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR
D002121:Calcium Channel Blockers; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D011188:Potassium; D009638:Norepinephrine