PT  - JOURNAL ARTICLE
AU  - K D Meisheri
AU  - G P Sage, 2nd
AU  - L A Cipkus-Dubray
TI  - Factors affecting rabbit mesenteric artery smooth muscle sensitivity to calcium antagonists.
DP  - 1990 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1167--1174
VI  - 252
IP  - 3
4099  - http://jpet.aspetjournals.org/content/252/3/1167.short
4100  - http://jpet.aspetjournals.org/content/252/3/1167.full
SO  - J Pharmacol Exp Ther1990 Mar 01; 252
AB  - 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.(ABSTRACT TRUNCATED AT 250 WORDS)