Losartan and atenolol on hypertension induced by adenosine receptor blockade

Auton Autacoid Pharmacol. 2003 Apr;23(2):133-40. doi: 10.1046/j.1474-8673.2003.00287.x.

Abstract

1. The prolonged infusion of 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), a non-selective antagonist of adenosine receptors, induces hypertension, an increase in plasma renin activity and morphological cardiovascular changes. 2. The aim of this work was to evaluate the effects of losartan, a selective AT1 receptor antagonist, and atenolol, a beta-adrenoceptor antagonist, on DPSPX-induced hypertension. 3. Male Wistar rats (250-300 g, n = 4-6) were treated for 1 or 4 weeks with: saline i.p.; DPSPX (90 microg kg(-1) h(-1)) i.p.; losartan (15 mg kg(-1) day(-1)) p.o.; atenolol (25 mg kg(-1) day(-1)) p.o.; DPSPX (90 microg kg(-1) h(-1)) i.p. + losartan (15 mg kg(-1) day(-1)) p.o.; DPSPX (90 microg kg(-1) h(-1)) i.p. + atenolol (25 mg kg(-1) day(-1)) p.o. Blood pressure was measured by the 'tail-cuff' method in conscious animals. Fragments of the mesenteric and tail arteries were processed for morphological study and the mean diameter of the vascular smooth muscle cells was determined. 4. DPSPX increased blood pressure. Losartan and atenolol prevented this rise but had no effect on blood pressure of control rats. DPSPX-treated groups showed hypertrophy of the vascular smooth muscle cells and proliferation of subintimal cells. Losartan but not atenolol prevented these changes. Losartan had no effect on the vascular morphology of control rats, while treatment with atenolol for 4 weeks induced hypertrophy of the vascular smooth muscle cells. 5. Both losartan and atenolol counteract the development of DPSPX-induced hypertension but only losartan prevents the alterations in vascular morphology.

MeSH terms

  • Administration, Oral
  • Adrenergic beta-1 Receptor Antagonists
  • Angiotensin II Type 2 Receptor Blockers
  • Animals
  • Atenolol / pharmacology*
  • Cell Division / drug effects
  • Disease Models, Animal
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Hypertension / chemically induced
  • Hypertension / drug therapy
  • Hypertension / prevention & control*
  • Infusion Pumps, Implantable
  • Infusions, Parenteral
  • Losartan / pharmacology*
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / pathology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / pathology
  • Myocardium / pathology
  • Purinergic P1 Receptor Antagonists*
  • Rats
  • Rats, Wistar
  • Receptor, Angiotensin, Type 2 / administration & dosage
  • Receptor, Angiotensin, Type 2 / drug effects
  • Receptors, Adrenergic, beta-1 / administration & dosage
  • Receptors, Adrenergic, beta-1 / drug effects
  • Receptors, Purinergic P1 / administration & dosage
  • Receptors, Purinergic P1 / drug effects
  • Renin / blood
  • Tail / blood supply
  • Tail / drug effects
  • Tail / pathology
  • Xanthines / administration & dosage
  • Xanthines / adverse effects
  • Xanthines / antagonists & inhibitors

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Angiotensin II Type 2 Receptor Blockers
  • Purinergic P1 Receptor Antagonists
  • Receptor, Angiotensin, Type 2
  • Receptors, Adrenergic, beta-1
  • Receptors, Purinergic P1
  • Xanthines
  • Atenolol
  • 1,3-dipropyl-8-(4-sulfophenyl)xanthine
  • Renin
  • Losartan