EFFECTS OF ENALAPRIL ON VASOACTIVE-INTESTINAL-PEPTIDE METABOLISM AND TISSUE-LEVELS

Angiotensin converting enzyme inhibitor therapy results in an increase in cardiac output without an increase in heart rate suggesting a posi tive inotropic effect. This cannot be explained by changes in angioten sin II and bradykinin concentrations. Angiotensin converting enzyme ma y also metabolise vasoactive intestinal peptide (VIP), a vasodilator a nd positive inotrope whose concentration in the heart declines in hear t failure. We sought to determine whether changes in plasma VIP or its metabolism might explain the positive inotropic effect of angiotensin converting enzyme inhibitors. We also measured VIP in the heart to de termine whether a local increase in VIP might explain this effect. Mal e Sprague-Dawley rats were randomised to control and enalapril groups (2 mg kg(-1) day(-1)). After 7 days, rats were anaesthetised and under went metabolic clearance studies for VIP or had hearts, lungs and kidn eys removed and snap frozen. VIP concentrations in plasma, infusate an d tissue extracts were measured by radioimmunoassay. Plasma concentrat ions of VIP were unchanged by treatment with enalapril (control: 7.7 /- 0.8 pmol l(-1); enalapril: 7.9 +/- 0.8 pmol l(-1)), while the metab olic clearance rate of VIP increased significantly (control: 10.4 +/- 1.4 ml min(-1) 100 g(-1); enalapril: 17.3 +/- 1.6 mi min(-1) 100 g(-1) ; P < 0.005) Secretion rate also increased in enalapril treated rats ( 139.1 +/- 25.0 pmol min(-1) 100 g(-1)) compared with controls (96.3 +/ - 13.4 pmol min(-1) 100 g(-1); P < 0.01). VIP in the heart increased a fter enalapril (control: 208.4 +/- 39.0 pmol g(-1); enalapril: 928.9 /- 123.6 fmol g(-1); P < 0.0005). Angiotensin converting enzyme inhibi tion increases the metabolism of VIP, However, the significant increas e in the myocardial concentration of VIP may contribute to the benefic ial haemodynamic inotrope effects of angiotensin converting enzyme inh ibitors. (C) 1998 Elsevier Science B.V. All rights reserved.