Faculty Collaboration Database

Effect of KT-362, a putative intracellular calcium antagonist, on norepinephrine-induced contractions and inositol monophosphate accumulation in canine femoral artery. J Cardiovasc Pharmacol 1989 Mar;13(3):502-7

Date

03/01/1989

Pubmed ID

2471898

DOI

10.1097/00005344-198903000-00020

Scopus ID

2-s2.0-0024582073 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

The purpose of the present study was to determine if the intracellular calcium antagonist, KT-362, inhibits norepinephrine- (NE) induced contractions and inositol monophosphate (IP) accumulation in canine femoral arteries preincubated with [3H]inositol. Norepinephrine dose-dependently increased contractile tension and produced a parallel stimulation of inositol phospholipid hydrolysis as measured by IP accumulation. This stimulation was inhibited by the selective alpha 1 adrenoceptor antagonist, prazosin (0.1 microM), indicating that the NE-induced stimulation of inositol phospholipid hydrolysis is coupled to alpha 1 adrenoceptor activation in canine femoral artery. Pretreatment with nitroglycerin (100 microM), 8-Br cyclic guanosine monophosphate (cGMP) (1 microM), or diltiazem (40 microM) inhibited contractile responses produced by NE; however, these agents had no significant effect on NE-induced IP accumulation. In contrast, pretreatment with KT-362 (10-100 microM) greatly inhibited both the NE-induced contractions and IP accumulation. KT-362 also produced a marked inhibition of NE-induced contractions in normal as well as zero calcium buffer, whereas diltiazem (40 microM) had no effect in zero calcium buffer. These results indicate that the mechanism of action of KT-362 differs from diltiazem, nitroglycerin, and 8-Br cGMP, and these data suggest that one of the mechanisms by which KT-362 antagonizes NE-induced vasoconstrictor responses is by decreasing inositol phospholipid hydrolysis in canine femoral artery.

Author List

Eskinder H, Hillard CJ, Wilke RA, Gross GJ

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Calcium Channel Blockers
Diltiazem
Dogs
Female
Femoral Artery
Inositol Phosphates
Male
Muscle, Smooth, Vascular
Myocardial Contraction
Nitroglycerin
Norepinephrine
Receptors, Adrenergic, alpha
Sugar Phosphates
Thiazepines
Vasoconstriction
Vasodilator Agents