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Remodeling of the rat right and left ventricles in experimental hypertension
1Cardiovascular Institute, Michael Reese Hospital, University of Chicago Pritzker School of Medicine, Ill.
Insights
In renovascular hypertension, ventricular hypertrophy is linked to pressure, but collagen accumulation is driven by angiotensin II and aldosterone. These hormones, not just pressure, promote fibrosis in both ventricles.
Area of Science:
- Cardiovascular Physiology
- Renal Hypertension
- Cardiac Fibrosis
Background:
- Pathological left ventricular hypertrophy (LVH) in renovascular hypertension involves collagen accumulation.
- The roles of arterial pressure versus circulating hormones like angiotensin II (AII) and aldosterone (AL) in this process are unclear.
Purpose of the Study:
- To investigate the independent contributions of ventricular loading and hormonal factors (AII, AL) to cardiac hypertrophy and fibrosis.
- To differentiate the regulation of myocyte and nonmyocyte compartments in the myocardium during hypertension.
Main Methods:
- Compared three experimental hypertension models in rats: renovascular hypertension (high AII/AL), infrarenal aorta banding (normal AII/AL), and chronic aldosterone infusion (low AII, high AL).
- Assessed interstitial and perivascular collagen accumulation in both left and right ventricles.
Main Results:
- Renovascular hypertension and chronic aldosterone infusion significantly increased interstitial collagen and perivascular fibrosis in both ventricles.
- Infrarenal aorta banding caused systemic hypertension and LVH but did not induce significant fibrosis.
- Myocyte hypertrophy correlated with ventricular loading, while collagen accumulation was regulated by AII and AL.
Conclusions:
- Ventricular loading is the primary driver of myocyte hypertrophy in experimental hypertension.
- Circulating angiotensin II and aldosterone, independently or together, regulate myocardial collagen accumulation in both ventricles.
- Myocyte and nonmyocyte cardiac compartments are differentially regulated in response to hypertensive stimuli.
Abstract:
Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles.