Reduced plasma volume and mesenteric vascular reactivity in obese Zucker rats

Abstract

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 l of 0.5%) showed that OZR had comparable blood volumes to LZR but lower blood volume-to-body weight ratio (3.4 Ϯ 0.2 ml/100 g) than LZR (5.7 Ϯ 0.2 ml/100 g, P Ͻ 0.05). Ganglionic blockade (mecamylamine, 4 mg/kg) in isoflurane-anesthetized rats produced larger decreases in arterial pressure in OZR compared with LZR (52 Ϯ 2 vs. 46 Ϯ 2 mmHg). Pressor responses to NE (0.01-10 g/kg) were exaggerated with doses analyzed by body weight but not analyzed by drug quantity. Pressor responses to PE (1-24 g/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.

Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats

“…Another possible explanation for the differences in changes in SNA vs. MAP for the RVLM, CVLM, and NTS could be related to a threshold effect due to changes in adrenergic vascular reactivity. The acute rises in MAP are primarily due to constriction of the mesenteric circulation, and the mesenteric arteries are less responsive to ␣-adrenergic stimulation in OZR (31). With antagonism of GABA A receptors in the RVLM, a 50% difference in the sympathetic response coincided with a 23% difference in the pressor response in OZR vs. LZR.…”

“…In adult obese Zucker rats (OZR), renal and splanchnic SNA and MAP are elevated (16,27) compared with age-matched lean Zucker rats (LZR). Furthermore, autonomic ganglionic blockade evokes a larger decrease in basal MAP in OZR than in LZR (31). Similarly, elimination of sympathetic vasomotor tone by inhibition of rostral ventrolateral medulla (RVLM), the primary source of drive for SNA, evokes a greater decrease in MAP in Sprague-Dawley rats made obese by a high-fat diet (40).…”

Reduced constrictor reactivity balances impaired vasodilation in the mesenteric circulation of the obese Zucker rat

“…Hemodynamic parameters were assessed in anesthetized rats under isoflurane anesthesia as described previously (14). Arterial pressure was measured by the advancement of a fluidAddress for reprint requests and other correspondence:…”

“…Hemodynamic parameters were assessed in anesthetized rats under isoflurane anesthesia as described previously (14). Arterial pressure was measured by the advancement of a fluid-filled catheter into the thoracic aorta, and the heart rate was derived from the pressure pulse with the use of a cardiotachometer (CSI).…”

“…We used the obese Zucker rat (OZR), a well-established model of obesity and insulin resistance, as our model (26). Relative to lean controls (LZR), the OZR display intestinal organomegaly, elevated total mesenteric blood flow, and similar blood flow normalized to tissue mass (14). In vitro vasodilation to the NO-dependent agonist acetylcholine was examined in mesenteric resistance arteries [Ͻ175 m inner diameter] to determine the effects of obesity on NO-mediated dilation.…”