Reduced plasma volume and mesenteric vascular reactivity in obese Zucker rats

Obese Zucker rats (OZR) are mildly hypertensive with an apparently elevated sympathetic vasomotor tone compared with lean Zucker rats (LZR). Studies have also suggested enhanced adrenergic pressor reactivity in OZR but assumed comparable baroreflexes, or blood volume-to-body weight ratio, to LZR. In 15-wk-old OZR and LZR, we measured plasma volume and vascular reactivity to norepinephrine (NE) and phenylephrine (PE) with doses evaluated by body weight and plasma volume. Plasma volume measured by dye dilution (Evans blue; 200 μl of 0.5%) showed that OZR had comparable blood volumes to LZR but lower blood volume-to-body weight ratio (3.4 ± 0.2 ml/100 g) than LZR (5.7 ± 0.2 ml/100 g, P < 0.05). Ganglionic blockade (mecamylamine, 4 mg/kg) in isoflurane-anesthetized rats produced larger decreases in arterial pressure in OZR compared with LZR (52 ± 2 vs. 46 ± 2 mmHg). Pressor responses to NE (0.01-10 μg/kg) were exaggerated with doses analyzed by body weight but not analyzed by drug quantity. Pressor responses to PE (1-24 μg/kg) showed no difference with doses analyzed by body weight, but, analyzed by drug quantity, OZR showed a slight decrease in pressor reactivity. PE-induced increases in vascular resistance were exaggerated in the hindlimb circulation of OZR, normal in the renal circulation, and attenuated in the mesenteric circulation. The timing of the peak pressor response to PE corresponded with the increase in mesenteric vascular resistance, followed by rises in hindlimb and renal resistance. These data suggest that systemic adrenergic pressor reactivity is not enhanced in OZR, despite exaggerated vascular reactivity in the hindlimb of the OZR.