Role of basal nitric oxide synthesis in vasoconstrictor hyporeactivity in the perfused rat hindlimb after myocardial infarction: effect of captopril

Objectives: The contribution of vascular changes to the development of hear t failure is largely unknown. In the present study, we evaluated endothelia l and vascular contractile function in the rat hindlimb vascular bed after myocardial infarction (MI), including the modulatory role of basal nitric o xide (NO) production and the effects of treatment with the angiotensin conv erting enzyme inhibitor captopril on vascular function. Methods: MI was ind uced in male Wistar rats by Ligation of the left coronary artery. Acetylcfi oline-induced dilatations were assessed in the ex vivo perfused hindlimb at various time points. At 2 and 5 weeks post-MI, vascular contractile functi on in the perfused hindlimb was assessed from resistance changes induced by 35 mM and 125 mM potassium (Ki) and the maximum increase in resistance (De lta R-max, 125 mM K+ and 3 mg phenylephrine). Basal NO synthesis was blocke d for 2 weeks with L-nitro-arginine methylester (L-NAME) in sham and MI rat s and similar contractility experiments were performed. The effect of capto pril treatment from 2 to 5 weeks post-MI on vasoconstrictor responses was a lso tested. Results: Acetylcholine-induced dilatations in the presence of 1 0 mu M indomethacin were not different between sham and MI rats. Vasoconstr ictor responses to K+ and Delta R-max were reduced at 2 weeks after MI. Thi s reduction in vasoconstrictor ability was similar to that seen in L-NAME-t reated sham rats, while chronic L-NAME treatment did not affect vasoconstri ctor reactivity in MI rats. Similarly, L-NAME induced an increase in mean a rterial pressure in sham rats, but not in MI rats. At 5 weeks after MI, vas oconstriction to 125 mM K+ and Delta R-max were still reduced in MI rats; t his response was however partially restored after captopril treatment. Conc lusion: The development of vascular contractile hyporeactivity in the rat h indlimb after MI may be due to reduced basal NO production. Delayed treatme nt with captopril improves peripheral vascular contractile function in this setting. (C) 1999 Elsevier Science B.V. All rights reserved.