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Abdulla MH, Sattar MA, Abdul Hye Khan M, Abdullah NA, Johns EJ;
2008
September
Acta Physiologica
Influence of sympathetic and AT(1)-receptor blockade on angiotensin II and adrenergic agonists-induced renal vasoconstrictions in spontaneously hypertensive rats.
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Aim: This study investigated the influence of angiotensin II receptor and adrenergic blockade on the renal vasoconstrictions caused by angiotensin II (Ang II) and adrenergic agonists in spontaneously hypertensive rats (SHR). Methods: Forty-eight SHR rats were subjected to 7 days of losartan (10 mg/kg/day p.o.), carvedilol (5 mg/kg/day p.o.) or losartan plus carvedilol (10 mg/kg/day + 5 mg/kg/day p.o.). On day 8, the rats were anesthetized and renal vasoconstrictor experiments performed. One group of rats underwent acute unilateral renal denervation. Results: There were significant (P<0.05) reductions in the renal vasoconstrictor responses to noradrenaline, phenylephrine, methoxamine and Ang II after losartan and carvedilol treatments compared to untreated rats (all P<0.05). However, in renally denervated SHR treated with carvedilol, the vasoconstrictor responses to all the vasoactive agents were enhanced compared to those in SHR with intact renal nerves treated with carvedilol. Intact SHR given both losartan and carvedilol showed greater renal vasoconstrictor responses to the vasoactive agents than when given either losartan or carvedilol alone (all P<0.05). Conclusion: Carvedilol reduced the vasoconstrictor response to Ang II and all the adrenergic agonists in the presence of the renal nerves but following removal of renal sympathetic activity, carvedilol enhanced the sensitivity of both renal alpha(1)-adrenoceptors and AT(1) receptors to the vasoactive agents. Co-treatment with losartan and carvedilol reduced the renal vasoconstrictor responses to exogenously administered vasoactive agents but to a lesser extent than losartan or carvedilol alone. The results obtained demonstrate an interaction between Ang II receptors and adrenergic neurotransmission in the SHR.
10.1111/j.1748-1716.2008.01895.x
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