Effects of chronic nitric oxide synthase inhibition on cerebral arterioles in Wistar-Kyoto rats.
OBJECTIVE
Cerebral arterioles in stroke-prone spontaneously hypertensive rats (SHRSP), but not in Sprague-Dawley rats with hypertension induced by nitric oxide (NO) synthase inhibition, undergo inward remodeling. The goal of this study was to determine whether development of vascular inward remodeling may depend on genetic factors.


METHODS
We examined effects of NO synthase inhibition on the structure of cerebral arterioles in Wistar-Kyoto rats (WKY), a rat strain genetically distinct from Sprague-Dawley.


METHODS
Pressure (servonull), diameter (cranial window) and cross-sectional area of the vessel wall (CSA, histologically) were measured in maximally dilated (EDTA) cerebral arterioles in WKY, untreated (n = 8) or treated for 3 months with the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg per day, n = 10) in the drinking water, and in untreated SHRSP (n = 7).


RESULTS
Treatment with L-NAME in WKY increased mean cerebral arteriolar pressure (69 +/- 7 versus 47 +/- 7 mmHg, P < 0.05) and pulse pressure (30 +/- 3 versus 17 +/- 1 mmHg, P < 0.05) to levels significantly lower than in SHRSP (98 +/- 5 and 35 +/- 1 mmHg respectively, P < 0.05). CSA was significantly greater in L-NAME-treated WKY and SHRSP than in untreated WKY (1692 +/- 50 and 1525 +/- 98 microm respectively, versus 1224 +/- 85, P < 0.05). External diameter was significantly less in L-NAME-treated WKY than in untreated WKY (119 +/- 5 versus 135 +/- 4 microm, P < 0.05) but significantly greater than in SHRSP (98 +/- 1 microm, P < 0.05).


CONCLUSIONS
Cerebral arterioles undergo hypertrophy and remodeling in WKY with L-NAME-induced hypertension. These findings suggest that genetic factors present in WKY and SHRSP may play a role in the development of vascular inward remodeling during chronic hypertension in rats.
Chillon
Jean-Marc
JM
Cardiovascular Research Group, Faculté de Pharmacie de l'Université Henri Poincaré-Nancy I, Nancy, France. chillon@pharma.uhp-nancy.fr
Baumbach
Gary L
GL
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester