Faculty Collaboration Database

Mechanism of cGMP contribution to the vasodilator response to NO in rat middle cerebral arteries. Am J Physiol Heart Circ Physiol 2002 May;282(5):H1724-31

Date

04/18/2002

Pubmed ID

11959637

DOI

10.1152/ajpheart.00699.2001

Scopus ID

2-s2.0-0036087769 (requires institutional sign-in at Scopus site)   43 Citations

Abstract

This study examined the mechanism by which cGMP contributes to the vasodilator response to nitric oxide (NO) in rat middle cerebral arteries (MCA). Administration of a NO donor, diethylaminodiazen-1-ium-1,2-dioate (DEA-NONOate), or 8-bromo-cGMP (8-BrcGMP) increased the diameter of serotonin-preconstricted MCA by 79 +/- 3%. The response to DEA-NONOate, but not 8-BrcGMP, was attenuated by iberiotoxin (10(-7) M) or a 80 mM high-K(+) media, suggesting that activation of K(+) channels contributes to the vasodilator response to NO but not 8-BrcGMP. The effects of NO and cGMP on the vasoconstrictor response to Ca(2+) were also studied in MCA that were permeabilized with alpha-toxin and ionomycin. Elevations in bath Ca(2+) from 10(-8) to 10(-5) M decreased the diameter of permeabilized MCA by 76 +/- 5%. DEA-NONOate (10(-6) M) and 8-BrcGMP (10(-4) M) blunted this response by 60%. Inhibition of guanylyl cyclase with 1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one (10(-5) M) blocked the inhibitory effect of the NO donor, but not 8-BrcGMP, on Ca(2+)-induced vasoconstriction. 8-BrcGMP (10(-4) M) had no effect on intracellular Ca(2+) concentration ([Ca(2+)](i)) in control, serotonin-stimulated, or alpha-toxin- and ionomycin-permeabilized vascular smooth muscle cells isolated from the MCA. These results indicate that the vasodilator response to NO in rat MCA is mediated by activation of Ca(2+)-activated K(+) channels via a cGMP-independent pathway and that cGMP also contributes to the vasodilator response to NO by decreasing the contractile response to elevations in [Ca(2+)](i).

Author List

Yu M, Sun CW, Maier KG, Harder DR, Roman RJ

Author

David Harder PhD, MS Emeritus Professor in the Physiology department at Medical College of Wisconsin

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

Acetylcholine
Animals
Calcium
Cell Membrane Permeability
Cyclic GMP
Endothelium, Vascular
Ionomycin
Male
Middle Cerebral Artery
Nitric Oxide
Nitric Oxide Donors
Peptides
Potassium Channels
Rats
Rats, Sprague-Dawley
Serotonin
Type C Phospholipases
Vasoconstriction
Vasodilation