α_1B-Adrenoceptors mediate adrenergically-induced renal vasoconstrictions in rats with renal impairment

Abstract

Aim: This study examined whether α 1B -adrenoceptors are involved in mediating adrenergically-induced renal vasoconstrictor responses in rats with pathophysiological and normal physiological states. Methods: Male Wistar Kyoto and spontaneously hypertensive rats were induced with acute renal failure or experimental early diabetic nephropathy by cisplatin or streptozotocin, respectively. Cisplatininduced renal failure was confirmed by impaired renal function and pronounced tubular damage. Experimental early diabetic nephropathy was confirmed by hyperglycemia, changes in physiological parameters, and renal function. The hemodynamic study was conducted on anesthetized rats after 7 d of cisplatin (renal failure) and 4 weeks of streptozotocin (experimental early diabetic nephropathy). Results: In the rats with renal failure and experimental early diabetic nephropathy, there were marked reductions in their baseline renal blood flow (P<0.01). The baseline mean arterial blood pressure was either unaltered or lower (all P>0.05) in the renal failure and experimental early diabetic nephropathy rats, respectively, as compared to their non-renal failure and non-diabetic nephropathy controls. In the rats with renal impairment, chloroethylclonidine caused either accentuation or attenuation (all P<0.01) of the renal vasoconstrictor responses elicited by the adrenergic stimuli. However, in the non-renal failure and in the non-diabetic nephropathy rats, chloroethylclonidine did not cause any alteration in such responses (P>0.05). Conclusion: This study demonstrated the presence of functional α 1B -adrenoceptors that mediated the adrenergically-induced renal vasoconstrictions in rats with renal impairment, but not in rats with normal renal function.

Downregulation of cystathionine γ lyase and endothelial nitric oxide synthase and reduced responsiveness of α1A adrenergic receptors in the kidneys of left ventricular hypertrophied Wistar Kyoto rats

“…The reduced renal vasoconstrictor responses to NA, PE, and ME during the saline phase of LVH WKY indicate that α 1 adrenergic receptor signaling cascades and/or vascular responsiveness are attenuated, which may be due to the downregulation of the CSE/H 2 S and eNOS/NO pathways. The blockade of α 1A adrenergic receptors by the low-dose 5-MeU in the control WKY group blunted the responses to NA and PE but did not affect the responses of NA and PE in LVH WKY, indicating that adrenergic receptors' responsiveness to these nonselective α 1A adrenoceptor agonists was altered by the induction of LVH (Khan et al, 2008). By contrast, the responses to ME, a relatively selective agonist (Arévalo-León et al, 2003), were unchanged in the WKY and LVH groups.…”

Functional contribution of α1D-adrenoceptors in the renal vasculature of left ventricular hypertrophy induced with isoprenaline and caffeine in Wistar–Kyoto rats

“…Previous studies have shown that different diseases could affect renal ␣ 1 -adrenoreceptors, leading to compromised function of the kidneys (Armenia et al 2004;Khan et al 2008a;Abdulla et al 2009). The contribution of all 3 subtypes of ␣ 1 -adrenoreceptors (␣ 1A , ␣ 1B , and ␣ 1D ) have been reported in other disease conditions (Zhu et al 1997;Armenia et al 2004;Khan et al 2008b;Abdulla et al 2011), which highlighted the functional importance of these receptors in different pathological states. This study investigated a WKY rat model of LVH induced with caffeine, which is clear from the increase in circulating levels of NA, and with isoprenaline, which is a non-selective ␤-adrenergic agonist with effects on both ␤ 1 -adrenoceptors in the heart and ␤ 2 -adrenoceptors in the peripheral tissues (Daly et al 1971;Collomp et al 1991;Bell et al 2001).…”

Inhibition of Ang II and renal sympathetic nerve influence dopamine‐and isoprenaline‐induced renal haemodynamic changes in normal Wistar–Kyoto and spontaneously hypertensive rats

“…Both agonists were given in ascending and descending manner so that each dose produced two responses. An interval of 15 min was allowed between each agonist to ensure complete washout of the drug (Khan et al. , 2007, 2008a,b; Abdulla et al.…”