Increased responsiveness to calcium agonist BAY k 8644 and calcium antagonist nifedipine in femoral arteries of spontaneously hypertensive rats.
Calcium (Ca2+) channel functions were compared in femoral arteries isolated from 6-week-old spontaneously hypertensive rats (SHR) and from age-matched normotensive Wistar-Kyoto (WKY) rats. BAY k 8644 (BAY), a dihydropyridine Ca2+ channel agonist, elicited a dose-dependent contraction in strips of SHR femoral arteries with a pD2 value of 8.55. Maximum contraction induced by this agonist (1 X 10(-7) M) was comparable to the maximum developed by KCl (K+) depolarization. BAY was less effective in eliciting a contraction in strips of WKY rat femoral arteries. Increased sensitivity to K+ was also observed in SHR femoral arteries. Contractile responses of SHR femoral arteries to BAY were antagonized competitively by nifedipine with a pA2 value of 8.36. When the effects of an elevation in the level of extracellular K+ on the contractile responses to BAY were determined in SHR and WKY rat femoral arteries, dose-response curves for BAY were not significantly different between the SHR and WKY rats. Femoral arteries from SHR, but not from WKY rats, relaxed when placed in a Ca2+-free solution. The addition of nifedipine (10(-10)-10(-7) M) to unstimulated strips produced a dose-dependent relaxation in femoral arteries from SHR, but not from WKY rats. These results suggest that (1) the increased responsiveness to BAY seen in SHR femoral arteries appears to occur because these arteries are more depolarized than WKY rat femoral arteries; and (2) BAY acts primarily on the same site, presumably the dihydropyridine receptors of the voltage-dependent Ca2+ channels, at which nifedipine acts.
Aoki
K
K
Second Department of Internal Medicine, Nagoya City University Medical School, Japan.
Asano
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D004336:Drug Antagonism; D005263:Femoral Artery / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine