Maternal separation diminishes α-adrenergic receptor density and function in renal vasculature from male Wistar-Kyoto rats

Adultrats exposed to maternal separation (MatSep) are normotensive but display lower glomerular filtration rate and increased renal neuroadrenergic drive. The aim of this study was to determine the renal alpha-adrenergic receptor density and the renal vascular responsiveness to adrenergic stimulation in male rats exposed to MatSep. In addition, baroreflex sensitivity was assessed to determine a component of neural control of the vasculature. Using tissue collected from 4-mo-old MatSep and control rats, alpha(1)-adrenergic receptors (alpha(1) - ARs) were measured in renal cortex and isolated renal vasculature using receptor binding assay, and the alpha-AR subtype gene expression was determined by RT-PCR. Renal cortical alpha(1)-AR density was similar between MatSep and control tissues (B-max = 44 +/- 1 vs. 42 +/- 2 fmol/mg protein, respectively); however, MatSep reduced alpha(1)-AR density in renal vasculature (Bmax = 47 +/- 4 vs. 62 +/- 4 fmol/mg protein, P < 0.05, respectively). In a separate group of rats, the pressor, bradycardic, and renal vascular constrictor responses to acute norepinephrine injection (NE, 0.03-0.25 mu g/mu l) were determined under anesthesia. Attenuated NE-induced renal vasoconstriction was observed in rats exposed to MatSep compared with control (P < 0.05). A third group of rats was infused at steady state with the alpha(1) agonist phenylephrine (10 mu g/min iv) and vasodilator sodium nitroprusside (5 mu g/min iv). The difference between the change in heart rate/mean arterial pressure slopes was indicative of reduced baroreflex sensitivity in MatSep vs. control rats (-0.45 +/- 0.04 vs. -0.95 +/- 0.07 beats center dot min(-1) center dot mmHg(-1), P < 0.05). These data support the notion that reduced alpha-adrenergic receptor expression and function in the renal vasculature could develop secondary to MatSep-induced overactivation of the renal neuroadrenergic tone.