Hydrochlorothiazide improves ventricular compliance and thus performance without reducing hypertrophy in renal artery stenosis in rats.

Abstract

The effect of hydrochlorothiazide (1 mg/kg per day) on left ventricular (LV) mass and systolic and diastolic function was investigated in two-kidney, one clip (2K1C) renovascular hypertensive rats. Hydrochlorothiazide was administered from 8 weeks, and LV mass and function were measured at 16 weeks after surgery to induce hypertension. Cardiac performance was determined from cardiac output, stroke volume (per 100 g of body weight), and stroke work (per gram of LV weight) versus LV end-diastolic pressure (LVEDP) and versus LV strain relations in anesthetized open-chest, ventilated rats. LV compliance was determined from the LVEDP versus strain relation. Strain was calculated from LV end-diastolic short-axis diameter values. Hydrochlorothiazide reduced systolic blood pressure in 2K1C rats to levels similar to those in sham-operated controls (sham) at 12 weeks after surgery. A reduced afterload failed to influence LV mass, as left LV hypertrophy developed to the same extent in treated 2K1C rats. 2K1C hypertension produced abnormal cardiac performance with altered cardiac output, stroke volume, and stroke work versus LVEDP relations (stroke work versus LVEDP, intercept of 2K1C versus sham,p<0.001). This was attributed to a decreased ventricular compliance (strain versus LVEDP, slope of 2K1C versus sham, p< 0.001). In contrast, hydrochlorothiazide improved ventricular compliance (strain versus LVEDP, slope of 2K1C versus 2K1C hydrochlorothiazide, p<0.01) and thus returned the stroke work versus LVEDP relation to sham values (intercept of 2K1C versus 2K1C hydrochlorothiazide, p< 0.001). We conclude that hydrochlorothiazide reduces blood pressure but not the development of ventricular hypertrophy in 2K1C rats. Although a reduced blood pressure did not produce regression of ventricular hypertrophy, it was associated with an improved ventricular compliance and thus performance. This study underscores the value of equating changes in ventricular hypertrophy with changes in cardiac function when the value of antihypertensive agents is being assessed. Received July 14, 1992; accepted in revised form December 15, 1992. Please note: After the manuscript was accepted, the authors sent a letter and revised manuscript because they discovered they had made a statistical error. The changes were sent to both reviewers. The manuscript with the revised changes was accepted January 27, 1993. ventricular performance. Studies on ventricular function in human hypertension are ethically limited by an inability to assess cardiac function over a range of controlled ventricular filling volumes and pressures. Abnormal ventricular systolic and diastolic functional changes in hypertensive heart disease may be detected only at controlled filling pressures.5 Therefore, improvement of ventricular function with hydrochlorothiazide may be detected only over a range of filling volumes and pressures. The effect of hydrochlorothiazide on cardiac performance at controlled filling volumes and pressures in hypertensive heart disease has not been investiga...

β-Adrenergic Activation Initiates Chamber Dilatation in Concentric Hypertrophy

“…4,16,17 None of the rats died during ISO or vehicle administration, and 1 untreated SHR died of an indeterminate cause at 16 months of age (not included in the above sample numbers). Noninvasive systolic blood pressures (SBPs) were measured as previously described 18 at regular periods throughout the study. Chronic ISO administration may produce an enhanced LV filling volume through ␤ 2 -AR-mediated vasodilation and/or sympathetic effects on the kidney and, consequently, mediate LV remodeling through indirect mechanisms (preload-induced changes).…”

Attenuation of Cardiac Failure, Dilatation, Damage, and Detrimental Interstitial Remodeling Without Regression of Hypertrophy in Hypertensive Rats

“…Of those rats that did not survive the study period and were not included in the sample numbers given, 8 untreated SHR died at between 23 and 26 months of age (2 of a respiratory pathogen and 6 with signs of heart failure), 2 WKY (1 untreated and 1 hydralazine treated) died of soft tissue tumors at variable time periods, and 2 untreated WKY died of a respiratory pathogen at variable time periods; no hydralazinetreated SHR died. Systolic blood pressure was measured as previously described 13 at regular periods throughout the study.…”

“…The surgery, instrumentation, experimental techniques, and calculations used in our current study have previously been described and validated. [12][13][14] LV end diastolic (LVED) radius was determined from the equation…”

Impact of gender on adrenergic-induced cardiac dilatation and systolic dysfunction in spontaneously hypertensive rats

“…As the wall thickens by parallel replication of sarcomeres (figure 1.1), concentric hypertrophy may reduce cardiac filling because of a reduced radius (Grossman et al 1975, & Norton et al 1993. Hence the diastolic pressure-volume curve would be left shifted compared to normal, and the volume at a pressure of 0 mm Hg (V 0 ) would be decreased (figure 1.1).…”