Effects of chronic nitric oxide synthase inhibition on cerebral arterioles in rats.
We examined the effects of nitric oxide (NO) synthase inhibition on the structure and mechanics of cerebral arterioles. We measured pressure, diameter, and cross-sectional area of the vessel wall (histologically) in maximally dilated cerebral arterioles in Sprague-Dawley rats that were untreated or treated for 3 months with the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg per day). Treatment with L-NAME increased cerebral arteriolar mean (87+/-6 versus 42+/-2 mm Hg, P<.05) and pulse (25+/-2 versus 13+/-2 mm Hg, P<.05) pressures, as well as cross-sectional area of the vessel wall (1839+/-70 versus 1019+/-58 microm2, P<.05) and external diameter (101+/-4 versus 87+/-2 microm, P<.05). These findings suggest that hypertension induced by NO synthase inhibition is accompanied by hypertrophy of the vessel wall and enlargement of cerebral arterioles in rats. To determine the role of cerebral arteriolar pulse pressure in hypertrophy of cerebral arterioles during inhibition of NO synthase, we measured the cross-sectional area of the vessel wall in rats treated with L-NAME that underwent unilateral carotid clipping. Unilateral carotid clipping failed to prevent increases in cross-sectional area of the vessel wall (1507+/-173 and 1613+/-148 microm2 in the clip and sham sides, respectively) in rats treated with L-NAME, even though increases in pulse pressure were prevented (16+/-1 and 27+/-1 mm Hg in the clip and sham sides, respectively, P<.05). These findings suggest that inhibition of NO synthase may promote hypertrophy of cerebral arterioles independently of increases in arteriolar pulse pressure.
Chillon
J M
JM
Department of Pathology, University of Iowa College of Medicine and Cardiovascular Center, Iowa City 52242, USA.
Ghoneim
S
S
Baumbach
G L
GL
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester