Faculty Collaboration Database

Influence of sympathetic and AT-receptor blockade on angiotensin II and adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive rats. Acta Physiol (Oxf) 2009 Mar;195(3):397-404

Date

02/03/2009

Pubmed ID

19183357

DOI

10.1111/j.1748-1716.2008.01895.x

Scopus ID

2-s2.0-59149101885 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

AIM: This study investigated the influence of angiotensin II (Ang II) receptor and adrenergic blockade on the renal vasoconstrictions caused by Ang II and adrenergic agonists in spontaneously hypertensive rats (SHR).

METHODS: Forty-eight SHR were subjected to 7 days of losartan (10 mg kg(-1) day(-1) p.o.), carvedilol (5 mg kg(-1) day(-1) p.o.) or losartan + carvedilol (10 mg kg(-1) day(-1) + 5 mg kg(-1) day(-1) p.o.). On day 8, the rats were anaesthetized 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 with that in 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 with 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 the 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.

Author List

Abdulla MH, Sattar MA, Khan MA, Abdullah NA, Johns EJ

MESH terms used to index this publication - Major topics in bold

Adrenergic Agonists
Adrenergic alpha-Antagonists
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Animals
Carbazoles
Drug Interactions
Hypertension
Kidney
Losartan
Male
Propanolamines
Rats
Rats, Inbred SHR
Renal Circulation
Sympathetic Nervous System
Vasoconstriction
Vasoconstrictor Agents