RESTRICTION OF NITRIC-OXIDE RATHER THAN ELEVATED BLOOD-PRESSURE IS RESPONSIBLE FOR ALTERATIONS OF VASCULAR-RESPONSES IN NITRIC OXIDE-DEFICIENT HYPERTENSION

The responsiveness of isolated high-pressure (aorta, renal artery) and low-pressure vessels (pulmonary artery) was compared during systemic hypertension induced by chronic inhibition of nitric oxide synthesis b y N-G-nitro-L-arginine methyl eater (L-NAME) in rats L-NAME (40 mg/kg/ day) was given to animals in their drinking water. After 4 weeks of L- NAME treatment, systolic blood pressure increased by 37 % as compared with that in the control group. Chronic L-NAME treatment resulted in s ignificant reduction of endothelium-dependent relaxation to acetylchol ine (10(-8) to 3x10(-6) mol/l) in both types of vessels The reduced re laxation was not influenced by acute pretreatment with indomethacin (1 0(-5) mol/l), however, it was further reduced by acute pretreatment wi th additional L-NAME (10(-4) mol/l). L-arginine (10(-4) mol/l) improve d the reduced relaxation. Endothelium-independent relaxation to sodium nitroprusside (10(9) to 10(-6) mol/l) was unaffected by L-NAME treatm ent. beta-adrenoceptor-mediated relaxation to isoprenaline (10(-8) to 3x10(-6) mol/l) was also not influenced by chronic L-NAME treatment. S imilar alterations in the responsiveness of high- and low-pressure ves sels indicate rather the decisive role of nitric oxide restriction tha n that of elevated blood pressure in their development.