Factors affecting rabbit mesenteric artery smooth muscle sensitivity to calcium antagonists

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 252; no. 3; pp. 1167 - 1174
• Main Authors: K D Meisheri, G P Sage, 2nd, L A Cipkus-Dubray
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.03.1990
• Subjects: Animals; arteries; Biological and medical sciences; calcium; Calcium - antagonists & inhibitors; Calcium - metabolism; Cardiovascular system; Dose-Response Relationship, Drug; Gallopamil - pharmacology; In Vitro Techniques; Medical sciences; Mesenteric Arteries; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Nifedipine - pharmacology; Norepinephrine - pharmacology; Pharmacology. Drug treatments; Potassium - metabolism; Rabbits; smooth muscle; Vasodilator agents. Cerebral vasodilators; Calcium; Calcium antagonist; Electrophysiology; Rabbit; Smooth muscle; Lagomorpha; In vitro; Vasodilation; Vertebrata; Mesenteric artery; Mammalia; Animal; Norepinephrine
• ISSN: 0022-3565; 1521-0103

The sensitivity of rabbit isolated superior mesenteric artery to Ca++ antagonists was examined under various conditions. Relaxation dose-response curves for D600 or nifedipine were generated, and IC50 values were calculated. In the first series of experiments, D600 or nifedipine IC50 was found to be 20-25-fold greater for norepinephrine (NE, 5 microM) contraction than for 80 nM K+ contraction. Even when the tissues were depolarized with 80 mM K+ before NE contraction, D600 or nifedipine IC50 still remained significantly greater compared with 80 mM K+ alone and remained closer to that during NE alone. Also a protocol was designed to study NE-induced phasic contraction in EGTA-physiological salt solution (a functional indicator of intracellular Ca++ release) as well as NE-induced sustained contraction after readdition of Ca++. The effects of varying [K+]ex (0-80 nM range) on NE-induced [Ca++]i release as well as on the D600 IC50 for NE contraction was studied. Increasing [K+]ex was found to enhance NE-sensitive [Ca++]i release and lower the D600 IC50 for NE contraction. Thus, conditions causing an increase in the ability of NE to cause [Ca++]i release were associated with an increase in the sensitivity of NE contraction to D600. These data provide functional evidence that the receptor-agonist sensitive Ca++ influx process in vascular smooth muscle is not solely regulated by changes in membrane potential. Additional mechanisms, such as a modulatory role of [Ca++]i release, in this process are implicated.