Abstract
The effectiveness of verapamil, diltiazem and nifedipine in reducing potassium-induced enhancement of vascular responses to norepinephrine was studied in rabbit aorta and porcine coronary arteries. At multiple levels of external potassium concentration (4-28 mM), norepinephrine concentration-response curves were performed. Whereas the tissue was only slightly depolarized (about 5 mV) by an increase in external potassium to 20 mM, the norepinephrine response was markedly potentiated. For example, the EC50 of norepinephrine in aortic rings was reduced from 4.7 X 10(-8) M in 4 mM potassium to 4.7 X 10(-9) M in 20 mM potassium. Calcium channel blockers reduced potassium- and calcium-induced contractions, the IC50 being 6 X 10(-8) M for verapamil, 5 X 10(-7) M for diltiazem and 3 X 10(-9) M for nifedipine. These concentrations only minimally reduced norepinephrine contraction in 4 mM potassium but virtually abolished the depolarization-induced potentiation of the norepinephrine contraction. Even short exposures to levels of potassium, which resulted in little or no contraction by themselves, markedly potentiated the norepinephrine contraction. Therefore, the abolition of this potentiation by calcium channel blockers cannot be explained by a reduction of potassium-induced contraction. Similar observations were made in porcine coronary arteries. Thus, the potency of calcium channel blockers against norepinephrine-induced contractions is markedly increased in depolarized vascular smooth muscle. Calcium channel blockers may be especially effective in preventing enhanced vascular contractions resulting from physiological concentrations of catecholamines in partially depolarized vascular smooth muscle.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|