Hemodynamic Alterations in Hypertensive Obese Rabbits

Abstract

There is little information on changes in overall and regional hemodynamics in obesity-associated hypertension. Therefore, the purpose of this study was to determine alterations in overall and regional blood flows and resistances in adipose and nonadipose tissues in a new model of obesity-associated hypertension in rabbits. Sixteen female New Zealand White rabbits were fed either a maintenance or high-fat diet; after 8 to 12 weeks cardiac output and regional blood flows were measured with the use of radioactive microspheres. Obese rabbits (5.22 +/- 0.14 versus 3.66 +/- 0.04 kg) had higher blood pressure (113 +/- 3 versus 95 +/- 1 mm Hg), cardiac output (812 +/- 59 versus 593 +/- 47 mL/min), and heart rate (269 +/- 12 versus 219 +/- 9 beats per minute) and lower overall peripheral resistance (0.14 +/- 0.01 versus 0.17 +/- 0.01 mm Hg/[mL/min]) than lean rabbits. Compared with lean controls, obese rabbits had higher weights of the ventricles, kidneys, liver, ovaries, adrenals, diaphragm, and spleen. Absolute blood flows were greater in the ventricles, kidneys, lungs, and ovaries, but differences were minimized when flows were normalized for organ weight. Adipose tissue flow per gram weight was significantly lower and resistance higher in obese rabbits. However, calculated total adipose tissue flow was higher in obese rabbits (86 versus 45 mL/min). Absolute resistances were lower in the left ventricle, kidneys, and large intestine, but when resistances were indexed for organ weight, kidney resistance tended to be higher in obese rabbits. These results indicate that even short periods of obesity-associated hypertension result in marked overall and regional hemodynamic changes.

Hydralazine as antihypertensive therapy in obesity-related hypertension

“…In contrast, hydralazine is commonly used as monotherapy in animal studies, but its side effects are often not reported. As some of the potential side effects of hydralazine (eg, tachycardia, RAS activation, and plasma volume expansion) are already exhibited in obesity, 9,23,24 we documented whether the use of hydralazine as antihypertensive therapy exacerbated these effects.…”

“…21,22,15,16 Use of hydralazine as antihypertensive therapy in an obesity-hypertension model is further complicated by the fact that potential side effects are similar to physiological changes often seen in obesity (e.g., tachycardia and activation of the reninangiotensin system (RAS)). 9,23,24 Therefore, the purposes of this study were two-fold. First, using the rabbit model, we sought to determine whether the use of hydralazine as an antihypertensive therapy would exacerbate cardiovascular and hormonal alterations already present in obesity.…”

Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

“…The increase in both fat and organ masses raises whole-body metabolic demands and thus regional blood flows. 3 In turn, cardiac output, the sum of all regional blood flows, increases ( þ 37% in obese rabbits), putting an additional work load on the heart. Although experimental models of high-output heart failure, following the opening of an arteriovenous fistula for example, usually require larger increases in cardiac output (two-to three-fold increase) for heart failure to develop, the contributing load of a moderately increased cardiac output, however, cannot be excluded.…”

“…In the last few years, [3][4][5][6][7][8] a new animal model of obesity, the rabbit fed a high-fat diet has allowed us to study many of the mechanisms of obesity-associated cardiovascular pathologies. Ad libitum access to high-fat diet for 8-12 weeks led to a more than three-fold increase in percent fat content determined by carcass analysis and lipid extraction, from 10% in lean rabbits to about 34% in obese rabbits.…”

“…Compared to lean rabbits, obese rabbits exhibit a higher 24-h blood pressure ( þ 15%) and heart rate ( þ 30%), 6 increased cardiac output, 3 cardiac diastolic dysfunction 5,10 and abnormal diurnal cardiovascular rhythms. 8 Obese rabbits also exhibit neurohormonal changes with hyperinsulinemia, elevated plasma triglyceride levels and increased activity of the sympathetic nervous system and the reninangiotensin system.…”