Alterations in the vasoreactivity of hypertensive rat aortic rings: role of nitric oxide and superoxide radicals.
OBJECTIVE
Present study was undertaken to investigate involvement of nitric oxide (NO) and superoxide radicals in the modulation of vasoreactivity in a model of renal hypertension.


METHODS
Hypertension was induced in the male Sprague Dawley rats by aortic banding just above the left kidney. Relaxation or contraction following cumulative addition of acetylcholine (Ach, 1 x 10(-8) to 1 x 10(-5) M) or phenylephrine (PE, 1 x 10(-8) to 1 x 10(-5) mol/l) was studied in the aortic rings obtained from sham operated normotensive, hypertensive and captopril pretreated rats. Ach and PE responses were taken in the presence or absence of NO synthase inhibitor (L-NAME; 1 x 10(-5) and 1 x 10(-4) mol/l). Spontaneous release of NO from the aortic rings was evaluated by studying the inhibition of adenosine diphosphate stimulated platelet aggregation, while superoxide radicals were estimated by cytochrome c reduction method.


RESULTS
Ach induced vasorelaxation in PE precontracted rings was impaired following 8 wk after aortic banding, while spontaneous release of NO remained unaffected. Captopril pretreatment restored the aortic ring responsiveness to Ach. An increase in the superoxide radical generation and PE induced contraction following L-NAME treatment in the hypertensive rat aortic rings was observed.


CONCLUSIONS
Attenuation in the Ach induced NO release and augmentation in the superoxide radical generation seems to play an important role in the modulation of vasoreactivity following renal hypertension in rats.
Hegde
L G
LG
Division of Pharmacology, Central Drug Research Institute, Lucknow, India.
Srivastava
P
P
Kumari
R
R
Dikshit
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects*
D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013481:Superoxides; D010656:Phenylephrine; D009569:Nitric Oxide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester