title: Influence of sympathetic and AT-receptor blockade on angiotensin II and adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive rats.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia. mdapharm78@yahoo.co.uk
authors.forename: M H
authors.initials: MH
authors.lastname: Abdulla
authors.forename: M A
authors.initials: MA
authors.lastname: Sattar
authors.forename: Md A H
authors.initials: MA
authors.lastname: Khan
authors.forename: N A
authors.initials: NA
authors.lastname: Abdullah
authors.forename: E J
authors.initials: EJ
authors.lastname: Johns
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D004347:Drug Interactions; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation; D019808:Losartan / Q000494:pharmacology; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D000322:Adrenergic Agonists; D000317:Adrenergic alpha-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D002227:Carbazoles; D011412:Propanolamines; D014662:Vasoconstrictor Agents; D000077261:Carvedilol; D000804:Angiotensin II; D019808:Losartan