Regional hemodynamics after chronic nitric oxide inhibition in spontaneously hypertensive rats.
BACKGROUND
Inhibition of nitric oxide (NO) synthase by L-arginine analogs is associated with elevation of blood pressure in rats. Because endothelium-dependent vasomotion in different vascular beds is not homogenous, the aim of this study was to characterize and compare regional hemodynamic responses in carotid, femoral, and renal vascular beds after chronic NO inhibition in spontaneously hypertensive rats. The possible role of circulating endothelin and renin angiotensin systems in mediating the effects of chronic NO inhibition was also studied.


METHODS
Systemic and regional hemodynamics, left ventricular mass, plasma renin activity, and plasma endothelin-1 were determined in control and Nomega-nitro-Larginine methyl ester (L-NAME)-treated (10 mg/kg/day, 4 weeks) spontaneously hypertensive rats.


RESULTS
L-NAME treatment increased arterial pressure and total peripheral and regional vascular resistance and decreased cardiac output, stroke volume, and regional blood flow. An increase in blood flow ratio and a decrease in vascular resistance ratio between carotid and renal as well as femoral and renal vascular beds in rats treated with L-NAME was found. Blood flow and vascular resistance ratios between femoral and carotid vascular beds remained unchanged. L-NAME increased plasma renin activity and left ventricular weight/body weight ratio, whereas plasma endothelin-1 was not modified.


CONCLUSIONS
The results of this study showed that the renal circulation seemed to be more sensitive to the effects of chronic NO inhibition than carotid and femoral vascular beds. Simultaneous activation of the renin angiotensin system may further potentiate cardiovascular effects of chronic NO inhibition. No evidence that circulating endothelin-1 plays a role in this model of hypertension was found.
Varagic
J
J
Institute for Medical Research, Belgrade, Yugoslavia.
Jerkic
M
M
Jovovic
D
D
Nastic-Miric
D
D
Adanja-Grujic
G
G
Markovic-Lipkovski
J
J
Lackovic
V
V
Radujkovic-Kuburovic
G
G
Kentera
D
D
D000809:Angiotensins / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D019332:Endothelin-1 / Q000097:blood; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000809:Angiotensins; D019332:Endothelin-1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester