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 r esponses to acute nitric oxide (NO) synthesis inhibition has not been studi ed in detail in healthy humans. The purpose of the present study was to inv estigate 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 heal thy subjects. Methods. Mean arterial blood pressure (MAP), renal plasma flow (RPF), glome rular filtration rate (GFR), sodium excretion (U-Na*V), and plasma levels o f renin, Ang II, ANP, BNP, and cGMP were assessed in 15 healthy sodium repl ete humans before and after acute L-NMMA treatment (3 mg/kg) on two occasio ns, i.e. after pretreatment with the Ang II type 1 receptor (AT-1) antagoni st candesartan cilexetil (CAND; 8 mg) or placebo in a double blind, randomi zed fashion. Renal haemodynamics were measured during water diuresis using renal clearances of [I-125]hippuran and [Cr-51]EDTA. Plasma hormones were m easured 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 o f L-NMMA were not affected significantly by pretreatment with CAND. The eff ects of L-NMMA on hormones were roughly similar on both occasions with a dr op 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 vasoc onstriction and sodium retention during acute lowering of NO activity in he althy man.