Altered reactivity to α2‐adenergic stimulation in the vasculature of the Obese Zucker rat

Abstract

Obesity is associated with marked changes in adrenergic vasoconstriction of the resistance circulation. Stimulation of α1 receptors with phenylephrine promotes increased hindlimb vascular resistance (HVR) and decreased mesenteric resistance (MVR) in obese Zucker rats (OZR). Effects of obesity on constrictor reactivity to α2 receptor stimulation are unknown. Anesthetized lean Zucker rats (LZR) and OZR were instrumented with arterial catheters and flow probes around the mesenteric and renal arteries and distal aorta to measure MVR, renal vascular resistance (RVR) and HVR. I.v. injections of clonidine caused drops in blood pressure consistent with the central actions of clonidine that were similar in LZR and OZR. To rule out central effects reactivity was evaluated after 2 mg/kg mecamylamine. Clonidine (0.05–5 μg) caused increases in HVR that were similar in OZR and LZR. However, increases in MVR were greater in OZR vs. LZR (62±5 vs. 49±6 % of basal) as were increases in RVR (10±2 vs. 25±7%). To determine if NO deficit explains increased constriction, experiments were repeated with 500 μg/kg L‐NAME. Increases in MVR (72±4 vs 73±6%) and RVR (11±2 vs. 25±8%) persisted suggesting a difference in reactivity to α2‐receptor stimulation rather than loss of buffering NO. Together, these data indicate that loss of α1 vasoreactivity in the splanchnic and renal beds may be offset by increases in α2 vasoreactivity. (HL076533‐03)