Norepinephrine-induced blood pressure rise and renal vasoconstriction are not attenuated by enalapril treatment in microalbuminuric IDDM

Abstract

Background. In non-diabetic subjects, an attenuated systemic norepinephrine (NE) responsiveness may contribute to the mechanisms of action of angiotensin-converting enzyme (ACE) inhibitor treatment. We determined whether ACE inhibitor treatment influences systemic and renal haemodynamic responsiveness to exogenous NE, as well as urinary albumin excretion during NE, in microalbuminuric insulin-dependent diabetic (IDDM) patients, representing a patient category that benefits by strict blood pressure control. Methods. In seven microalbuminuric IDDM patients, systemic and renal responsiveness to NE, infused at individually determined threshold [Δmean arterial pressure (MAP) = 0 mmHg], 20% pressor (ΔMAP = 4 mmHg) and pressor (ΔMAP = 20 mmHg) doses, were compared before and after 8 weeks treatment with enalapril, 10 mg daily. Blood glucose was clamped at 5 mmol/l and insulin was infused at 30 mU/kg/h. Results. Enalapril decreased MAP (P < 0.05) and microalbuminuria (P < 0.05), whereas effective renal plasma flow (ERPF) increased (P < 0.01) and glomerular filtration rate remained unaltered. The filtration fraction tended to decline (P = 0.09). The ACE inhibitor-induced fall in MAP disappeared at NE pressor dose, and the overall mean increase in MAP in response to NE was even higher with than without enalapril (P < 0.05). After enalapril, the ERPF remained higher at all NE doses (P < 0.05), but the magnitude of the NE-induced fall in ERPF was not altered by ACE inhibition treatment. Overnight urinary albumin excretion fell with ACE inhibition (P < 0.05), but this effect was not seen during NE infusion. The angiotensin II/active renin ratio and serum aldosterone levels remained lower with enalapril at all NE doses (P < 0.05). Conclusions. Enalapril does not attenuate systemic and renal vascular responsiveness to exogenous NE in microalbuminuric IDDM despite adequate inhibition of the renin-angiotensin-aldosterone system. These findings suggest that the effect of NE on vasoconstriction is not counteracted effectively by ACE inhibition treatment alone.