AGING AND HUMAN HORMONAL AND PRESSOR RESPONSIVENESS TO ANGIOTENSIN-II INFUSION WITH SIMULTANEOUS MEASUREMENT OF EXOGENOUS AND ENDOGENOUS ANGIOTENSIN-II

A decline in the function of the renin angiotensin aldosterone system may induce adaptive changes in response to angiotensin II (ANG II) with age. We have examined platelet ANG II receptor density, blood pressure and aldosterone responses to ANG II [Asn1, Val5-ANG II] (Hypertensin, Ciba Geigy, Horsham, Sussex, England) infusion in 8 young, 24 to 30 years, and 8 older, 54 to 65 years, healthy volunteers. To measure circulating ANG II, we established a new method for specific and simultaneous measurement of exogenous [Asn1, Val5] (Hypertensin) and endogenous [Asp1, Ile-5] ANG II in plasma by using isocratic HPLC and radioimmunoassays with cross-reacting antibodies and compared results with immunoreactive ANG II which was measured conventionally using monoclonal antibodies. Baseline endogenous ANG II (Asp1, Ile-5-ANG II) levels in venous plasma were marginally, but not significantly, lower in the old [mean (95% confidence limits): 3.4 (< 0.1 to 7.7) v 3.7 (1.2 to 6.2), fmol/mL] and during suppression by the Hypertensin infusion appeared consistently, but not significantly, lower in the old [0.9 (0 to 3.1) v 2.1 (0.6 to 3.7), after 3 ng/kg/min], while the same infusion rate in young and old resulted in similar plasma Hypertensin levels. Baseline systolic blood pressure (SBP) was similar in both groups but the percentage increases in SBP at infusion rates of 1, 3.0, and 10 ng/kg/min were greater in the old than in the young (9.1 v 2.8, P < .05; 16.3 v 8.0, P < .01; 30.4 v 14.0% P < .001, respectively). The increment in diastolic blood pressure or mean arterial pressure during infusion did not differ significantly between the groups. Heart rate fell significantly during ANG II infusion in young (P < .05) but not old subjects. Basal plasma aldosterone was similar in both groups. However, the percentage increases in plasma aldosterone were greater in young than old at infusion rates of 1.0, 3.0, and 10.0 ng/kg/min (94 v - 5, 238 v 28; 462 v 69%, all P < .001). Platelet ANG II receptor density was elevated in the old [6.5 (1.9 to 11.1) v 1.14 (0.21 to 2.07), fmol/10(9) cells, P < .01]. Our findings demonstrate that it is possible to measure specifically and simultaneously exogenous and endogenous ANG II in plasma during Hypertensin infusion and that endogenous ANG II concentrations decrease with increasing levels of exogenous ANG II. During infusion, similar plasma Hypertensin levels were attained in both young and old, but systolic blood pressure responsiveness was increased in the old, while adrenal responsiveness was reduced.