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Effects of hypoxia on the vasodilator activity of nifedipine and evidence of secondary pharmacological properties

Broadley, Kenneth and Penson, Peter E. 2006. Effects of hypoxia on the vasodilator activity of nifedipine and evidence of secondary pharmacological properties. European Journal of Pharmacology 536 (3) , pp. 279-286. 10.1016/j.ejphar.2006.02.039

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The effects of hypoxia on the vasodilator response of endothelium-denuded rat aortic rings to the calcium channel blocker, nifedipine, were examined. Under normoxic conditions, nifedipine (10− 8–3 × 10− 6 M) attenuated the contractility of noradrenaline precontracted rings in a concentration-dependent manner, although the sensitivity was less than what occurs with K+ precontracted tissues. Under hypoxic conditions there was no relaxation by nifedipine. When a concentration–response curve to noradrenaline was constructed before and in the presence of a high concentration of nifedipine (10− 5 M), the response to noradrenaline was unaffected in both normoxic and hypoxic conditions. When noradrenaline was replaced by phenylephrine (10− 8–10− 5 M), the maximum tension was reduced in the presence of nifedipine to 59 ± 6% of the pre-nifedipine value. Repetition of the experiment in the presence of cocaine (10− 5 M) revealed the inhibitory effect of nifedipine on noradrenaline-induced contraction, the maximum contraction in the presence of nifedipine falling significantly (P < 0.005) to 67 ± 6% of the pre-nifedipine response. When propranolol (10− 7 M) was present in the bath, the maximum contraction to noradrenaline was significantly (P < 0.05) reduced by nifedipine to 55 ± 4% of its previous value. The fact that nifedipine was able to inhibit phenylephrine-induced contractions and relax noradrenaline-precontracted aortic rings confirms its calcium channel blocking activity. The failure to inhibit noradrenaline when added prior to the noradrenaline-induced contractions suggests an opposing effect in addition to calcium channel blockade, which cancels out the attenuation of noradrenaline — but not phenylephrine-induced contractions. When neuronal uptake of noradrenaline was blocked with cocaine or β-adrenoceptors were blocked with propranolol, the inhibitory effect of nifedipine against noradrenaline-induced contractions was revealed. This suggests that the additional property was due to blockade of neuronal reuptake or antagonism at β-adrenoceptors. This study also showed that nifedipine is ineffective as a vasodilator in the rat aorta under hypoxic conditions.

Item Type: Article
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: Aorta; Nifedipine; Hypoxia; Noradrenaline; Phenylephrine
Publisher: Elsevier
ISSN: 0014-2999
Last Modified: 04 Jun 2017 03:01

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