Effect of different drug classes on reverse remodeling of intramural coronary arterioles in the spontaneously hypertensive rat

Abstract

Background: Symptoms and signs of myocardial ischemia in the absence of obstructive coronary disease are common in hypertensive patients. This can be explained by CMD due to adverse remodeling of coronary arterioles which have also been reported in the SHR.

Objective: The aim of this study was to compare the effects of ramipril, perindopril, candesartan, atenolol, amlodipine, indapamide, and HMR1766 on CMD in the SHR.

Methods: Eight groups of 24-wk-old SHR were treated for 8 wk. BP was measured invasively at the end of the treatment. After sacrifice, hearts were mounted on a Langendorff apparatus for the measurement of hyperemic CF. Hearts were then processed for histomorphometric analysis.

Results: All compounds, except HMR1766, induced a significant reduction in BP. Perindopril and candesartan increased hyperemic CF, whereas the other compounds had no significant effect. Perindopril, ramipril, atenolol, indapamide, and HMR1766 induced significant reverse arteriolar remodeling, whereas candesartan and amlodipine did not.

Conclusions: The effect of antihypertensive treatment on CMD is not exclusively dependent on BP reduction. Compounds with comparable antihypertensive efficacy may exert different effects on CF and induce different degrees of reverse arteriolar remodeling.

Keywords: SHR; antihypertensive drugs; coronary blood flow; coronary microcirculation; hypertension; vascular remodeling.