CAFFEINE ATTENUATES THE RENAL VASCULAR-RESPONSE TO ANGIOTENSIN-II INFUSION

Non-modulation has been proposed as an intermediate phenotype in human essential hypertension. The trait is characterized by blunted aldoste rone and renal plasma flow responses to short-term angiotensin II (Ang II) infusion. Elevated tissue Ang II levels or decreased tissue adeno sine levels could account for this decreased sensitivity to Ang II. In support of the latter possibility, endogenous adenosine has been show n to contribute to the renal vasoconstrictive response to Ang II in an imals. We therefore tested the hypothesis that endogenous adenosine co ntributes to modulation of renal plasma flow in sodium-replete humans. We examined the effect of long-term administration of the adenosine r eceptor antagonist caffeine on baseline renal plasma flow and on the r enal plasma how response to short-term Ang II infusion in six salt-rep lete normotensive subjects in a single-blind, placebo-controlled study . para-Aminohippurate clearance was used to assess renal plasma flow. Ang II was infused in graded doses (0.3 to 3 ng/kg per minute) in the presence and absence of caffeine (250 mg P circle dot TID for 7 days). Blood pressure, plasma renin activity, Ang II, electrolytes, and para -aminohippurate clearance were measured before and after each dose of Ang II. Caffeine did not alter either baseline blood pressure or the b lood pressure response to Ang II but did increase baseline plasma reni n activity from 0.72+/-0.09 to 1.42+/-0.26 ng angiotensin I/mL per hou r (P=.01). Caffeine decreased the baseline renal plasma flow from 553/-38 to 476+/-31 mL/min per 1.73 m(2) (P=.004) and attenuated the rena l plasma flow response to a 3 ng/kg per minute infusion of Ang II (-10 6.5+/-25.2 versus -170.5+/-18 mL/min per 1.73 m(2), P=.006). These dat a demonstrate that caffeine modulates baseline renal plasma flow and t he renal plasma flow response to exogenous Ang II and therefore suppor t the hypothesis that adenosine contributes to modulation of renal pla sma flow in salt-replete humans. Thus, non-modulation may be partially acquired, and caffeine consumption must be controlled in studies that define modulation phenotype.