Endogenous and exogenous coronary vasodilatation are attenuated in cardiachypertrophy: a morphological defect?

Reactive hyperaemia (RH) following brief ischaemia is reduced in hypertroph ied hearts, and this may contribute to reduced coronary now reserve. We stu died vasodilatation during RH and in response to exogenous stimuli in contr ol and hypertrophied hearts and explored the mechanisms underlying RH. Vasc ular reactivity was assessed in isolated hypertrophied hearts (55 +/- 3 day s after aortic banding or sham operation) by constructing dose-response cur ves to acetylcholine (ACh), sodium nitroprusside (SNP) and adenosine. React ive hyperaemic vasodilatation was assessed after global ischaemia (5-120 s) in the presence/absence of L-NAME, 8-phenyltheophylline (8-PT) and glibenc lamide, Purine release and NO overflow in the coronary perfusate were analy sed. Aortic constriction increased heart/body weight ratio (47%), myocyte s ize (19%) and arteriolar wall thickness (51%), all P<0.01. Coronary reserve was reduced in hypertrophy (105 +/- 8% v 182 +/- 12%, P<0.01). Dose respon se curves for ACh, SNP and adenosine were reduced in hypertrophy (69%, 86% and 68%, all P<0.01) v shams; however ED50 values were unchanged. The peak flow and duration of RH were also attenuated (50%, P<0.001) in hypertrophy. While purine washout during RH was related to the duration of preceding is chaemia, nitrate washout was not. RH experiments in the presence of L-NAME, 8-PT and glibenclamide indicated that RHI is mediated by combined actions of K-ATP channels>adenosine>NO in both groups. RH is mediated by similar me chanisms in control and hypertrophied hearts. All vasodilatation was simila rly attenuated in hypertrophy, independent of endothelial activation. We hy pothesize that increased arteriolar wall thickness map limit vasodilator re sponses to all stimuli in hypertrophy. (C) 2000 Academic Press.