Peroxynitrite reduces vasodilatory responses to reduced intravascular pressure, calcitonin gene-related peptide, and cromakalim in isolated middle cerebral arteries.
Vasodilatory responses to progressive reductions in intravascular pressure or to calcitonin gene-related peptide (CGRP) or cromakalim were determined in rodent middle cerebral arteries (MCAs) before and after treatment with peroxynitrite (ONOO-). Middle cerebral artery diameters in isolated, pressurized MCAs were measured as intravascular pressure was reduced from 100 to 20 mm Hg in 20-mm Hg increments before and after inactive ONOO-, pH-adjusted ONOO-, or 10, 20, or 40 micromol/L ONOO- was added to the bath. In other MCAs, responses to CGRP (1 x 10-9 - 5 x 10-8) or cromakalim (3 x 10-8 - 8 x 10-7) were measured before and after the addition of 25 micromol/L ONOO-. Inactive ONOO- (n = 6, P = 0.40), pH-adjusted ONOO- (n = 6, P = 0.29), and 10 micromol/L ONOO- (n = 6, P = 0.88) did not reduce vasodilatory responses to reduced intravascular pressure. Middle cerebral arteries treated with 20 (n = 6, P < 0.0001) and 40 (n = 6, P > 0.0001) micromol/L ONOO- constricted significantly when intravascular pressure was reduced. Vasodilatory responses to CGRP or cromakalim were reduced by ONOO- (P > 0.02, n = 6 and P > 0.01, n = 7, respectively). ONOO- had no effect on vasoconstriction in response to serotonin or vasodilation in response to KCl. These studies demonstrate that ONOO- reduces multiple cerebral vasodilatory responses.
DeWitt
D S
DS
Charles R. Allen Research Laboratories, Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-0591, USA.
Mathew
B P
BP
Chaisson
J M
JM
Prough
D S
DS
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D019806:Cromakalim / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D007022:Hypotension / Q000503:physiopathology; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology*; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D005609:Free Radicals; D009566:Nitrates; D016877:Oxidants; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; C039642:peroxynitric acid; D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide