Alpha-adrenoceptor-mediated vasoconstriction is not involved in impaired functional vasodilation in the obese Zucker rat

Abstract

1. Obesity/metabolic syndrome is associated with augmented a-adrenoceptor sensitivity and impaired hyperaemic responses to exercise. Thus, it is possible that this elevated a-adrenoceptor constriction contributes to the blunted hyperaemic response. 2. Male lean and obese Zucker rats were instrumented for acute measurements of blood pressure (BP) and iliac blood flow (BF). Changes in BP and BF were determined in anaesthetized animals in response to intravenous administration of increasing doses of the a(1)-adrenoceptor agonist phenylephrine (PE). Once BF and BP returned to normal, a single bolus of the a-adrenoceptor antagonist phentolamine (0.5 mg) was administered. In separate animals, the spinotrapezius muscle was exteriorized for direct in situ observation of the microcirculation in response to phentolamine and muscle contraction. 3. Administration of PE demonstrated that iliac BF is highly autoregulated in the face of increasing perfusion pressure. Iliac conductance following phentolamine was significantly greater in obese rats. Following phentolamine administration, iliac vascular conductance was significantly greater in obese rats compared with lean animals. However, a-adrenoceptor blockade did not significantly alter arteriolar diameter in the spinotrapezius muscle during muscle contraction in either lean or obese animals. 4. These results suggest a greater contribution of the a-adrenoceptors in basal hindlimb vascular tone in obese rats. Furthermore, an augmented a-adrenoceptor-mediated vasoconstriction may not contribute to the impaired functional dilation in anaesthetized obese rats.

Fig. 1

(a) Blood pressure and (b) changes in blood pressure in response to graded infusions of phenylephrine (PE) in lean (n = 5; ○) and obese (n = 5; ●) rats. Data are presented as the mean±SEM. *P < 0.05 compared with obese rats.

Fig. 2

Iliac (a) blood flow and (b) conductance in response to graded infusions of phenylephrine (PE) in lean (n = 5; ○) and obese (n = 5; ●) rats. Data are presented as the mean±SEM. *P < 0.05 compared with baseline for lean and obese combined (main effect of dose); ^†P < 0.05 compared with 30 μL/min PE for lean and obese combined; ^‡P < 0.05 comapred with baseline and 15 and 30 μL/min PE for lean and obese combined.

Fig. 3

Baroreflex responses to phenylephrine are blunted in obese rats (●) compared with lean (○) animals. Data are presented as the mean±SEM (n = 5/group).

Fig. 4

Effect of α-adrenoceptor blockade on iliac vascular conductance in lean (□) and obese (■) rats. Data are presented as the mean±SEM (n = 5 per group). Inset: raw trace of the blood pressure response to phentolamine. *P < 0.05 compared with baseline; ^†P < 0.05 compared with lean rats after phentolamine administration (P < 0.05).

Fig. 5

Effect of α-adrenoceptor inhibition on functional vasodilation in lean and obese rats. The spinotrapezius muscle was treated with phentolamine (10 μmol/L; ■;) for 30 min. (□), control. Data are presented as the mean±SEM (n = 4 per group). *P < 0.05 compared with lean control.

Fig. 6

Vasodilation in response to contraction of the spinotrapezius muscle in anaesthetized lean and obese Zucker rats. (a) Functional vasodilation of arterioles in the spinotrapezius muscle prior to phentolamine administration in lean and obese rats. (b) Changes in arteriole diameter in response to muscle contraction (■;) and phentolamine + muscle contraction () in the spinotrapezius muscle of lean and obese rats. (□), baseline. Arterioles were pretreated with SQ29548 (10 μmol/L) for 30 min. Data are presented as the mean±SEM (n = 4 per group). *P < 0.05 compared with lean control; †P < 0.05 compared with baseline. Bars indicate maximal diameter (10 μmol/L adenosine induced).