Hydralazine as antihypertensive therapy in obesity-related hypertension

The objectives were two-fold: (1) determine whether the use of hydralazine as antihypertensive therapy during obesity development exacerbated obesity-related cardioacceleration and hormonal abnormalities; (2) determine whether the absence of hypertension in obesity attenuated obesity-related abnormalities in hemodynamics, cardiac hypertrophy, and hormonal profile.

Female New Zealand White rabbits were divided into lean control (n=12), lean hydralazine-treated (n=9), obese control (n=11), and obese hydralazine-treated (n=8) groups. Pretreatment mean blood pressure (BP) and heart rate (HR) were determined using telemetry. Pretreatment BP was maintained during 12 weeks of obesity development using hydralazine.

Chronically measured BP and HR; plasma/blood volume; wet and dry ventricular weights; body fat/water; and hormonal profile (plasma renin activity, aldosterone, cortisol, atrial natriuretic peptide, adrenaline, and noradrenaline).

Hydralazine treatment in obese animals attenuated obesity-related renin-angiotensin system (RAS) activation. In contrast, RAS was activated in lean hydralazine, as indicated by increased plasma aldosterone. The absence of hypertension in obese hydralazine did not result in attenuation of cardioacceleration, cardiac hypertrophy, or intravascular volumes.

Hydralazine treatment in obese rabbits did not exacerbate obesity-related cardiovascular and hormonal alterations. Cardioacceleration and cardiac hypertrophy persisted in obese hydralazine despite BP control, suggesting hypertension-independent effects of obesity on these variables. Hydralazine's effects on RAS activation differed in lean and obese rabbits, suggesting that the systemic effects of hydralazine as a control therapy in evaluation of antihypertensive medications may differ depending on the underlying pathology.