Persistent hypertension following inhibition of nitric oxide formation in the young Wistar rat: role of renin and vascular hypertrophy.
OBJECTIVE
To determine whether induction of arterial hypertension in young normotensive Wistar rats by chronic inhibition of nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME) produced a form of self-sustained hypertension, and to investigate the role of the renin-angiotensin system and vascular hypertrophy in the hypertensive process.


METHODS
Three-week-old Wistar rats were given 100 or 40 mg/kg per day L-NAME or 40 mg/kg per day L-NAME plus 100 mg/kg per day captopril in their drinking water for between 4 and 7 weeks. Systolic blood pressure was measured by tail-cuff plethysmography both during treatment and after the treatment had been stopped. The effect of treatment on plasma renin was measured and the effect of treatment on mesenteric resistance artery structure was determined using a small-vessel myograph.


RESULTS
L-NAME produced a progressive and marked increase in blood pressure during the period of treatment. Hypertension was sustained for 14 weeks after stopping treatment. L-NAME resulted in a fourfold increase in plasma renin which remained elevated after treatment was stopped. Blood pressure was correlated with plasma renin levels. Treatment with L-NAME plus captopril markedly attenuated the rise in blood pressure and captopril also produced a marked fall in blood pressure in rats that developed persistent hypertension. Rats with self-sustained hypertension exhibited both cardiac and mesenteric resistance vessel hypertrophy. The induction of vascular hypertrophy with low-dose L-NAME did not result in the development of self-sustained hypertension.


CONCLUSIONS
Chronic L-NAME treatment in young rats can produce a form of persistent hypertension which is renin-dependent and which does not seem to involve a vascular amplifier mechanism.
Morton
J J
JJ
MRC Blood Pressure Unit, Western Infirmary, Glasgow, UK.
Beattie
E C
EC
Speirs
A
A
Gulliver
F
F
D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000473:pathology*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D006984:Hypertrophy; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000502:physiology*
D009569:Nitric Oxide; D001120:Arginine; D002216:Captopril; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester