Hydralazine as antihypertensive therapy in obesity-related hypertension.
OBJECTIVE
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.


METHODS
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Carroll
J F
JF
Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. jcarroll@hsc.unt.edu
King
J W
JW
Cohen
J S
JS
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use* / Q000633:toxicity; D001699:Biometry; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006830:Hydralazine / Q000627:therapeutic use* / Q000633:toxicity; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D011817:Rabbits; D012084:Renin-Angiotensin System / Q000187:drug effects
D000959:Antihypertensive Agents; D006728:Hormones; D006830:Hydralazine