The systemic and renal response to NO inhibition is not modified by angiotensin-II-receptor blockade in healthy humans

Background. The role of angiotensin II (Ang II) in the systemic and renal responses to acute nitric oxide (NO) synthesis inhibition has not been studied in detail in healthy humans. The purpose of the present study was to investigate the effects of Ang II receptor blockade on the systemic and renal response to acute treat ment with Ng-monomethyl-L-arginine (L-NMMA) in healthy subjects. Methods. Mean arterial blood pressure (MAP), renal plasma flow (RPF), glomerular filtration rate (GFR), sodium excretion (U-Na*V), and plasma levels of renin, Ang II, ANP, BNP, and cGMP were assessed in 15 healthy sodium replete humans before and after acute L-NMMA treatment (3 mg/kg) on two occasions, i.e. after pretreatment with the Ang II type 1 receptor (AT-1) antagonist candesartan cilexetil (CAND; 8 mg) or placebo in a double blind, randomized fashion. Renal haemodynamics were measured during water diuresis using renal clearances of [I-125]hippuran and [Cr-51]EDTA. Plasma hormones were measured by radioimmunoassays. Results. On both study days L-NMMA treatment induced a significant increase in MAP and a significant decrease in GFR, RPF, and U-Na*V. These effects of L-NMMA were not affected significantly by pretreatment with CAND. The effects of L-NMMA on hormones were roughly similar on both occasions with a drop in P-cGMP and U-cGMP. However, a fall in renin was observed only during CAND pretreatment. Conclusions. We conclude that Ang II is not a major mediator of acute vasoconstriction and sodium retention during acute lowering of NO activity in healthy man.