The effect acute unilateral renal denervation on renal vasoconstrictions in spontaneously hypertensive rats (SHR) treated with a combination of carvedilol and losartan

Abstract

Interactions between the renin‐angiotensin (RAS) and sympathetic nervous systems (SNS) were investigated by examining the influence of acute renal denervation and adrenergic and AT1 receptor blockade in SHR. Thirty (n=30) SHR treated with a combination of carvedilol plus losartan (5 mg/kg p.o + 10 mg/kg, p.o.) for 7 days. On day 8, the rats were anaesthetized and the left kidney was denervated or left intact. The renal vasoconstrictor responses to intrarenal doses of noradrenaline (NA), phenylephrine (PE) and Angiotensin II (Ang II) were determined. Data, mean±SEM were subjected to ANOVA with significance at P<0.05. The magnitudes of the vasoconstrictor responses to NA, PE and Ang II at 50%, 48% and 35% in the control rats were decreased to 44%, 43% and 8% respectively (all P<0.05), after treating them with losartan+carvedilol. However, following renal denervation, the vascular responsiveness to Ang II and adrenergic agonists was blunted to 50% (P<0.05) of their values in rats with intact renal nerves treated with this drug combination. Collectively, these data demonstrate an important influence of the renal sympathetic nerves on the ability of carvedilol and losartan to block renal vasoconstrictions in the SHR and point to an important interaction between Ang II, adrenergic vasoconstriction and the renal nerves.