Losartan and atenolol on hypertension induced by adenosine receptor blockade

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.

Xanthine Oxidase Inhibition by 1,3-dipropyl-8-sulfophenyl-xanthine (DPSPX), an Antagonist of Adenosine Receptors

“…This pressor system is activated in this model, as shown previously by the higher plasma renin activity 3,4 and higher angiotensin II plasma levels 5 , thus contributing to the development and maintenance of the hypertension induced by DPSPX. This is further supported by the fact that angiotensin-converting enzyme inhibition 3,4 and angiotensin II receptor antagonism 6 prevented the rise in blood pressure and the alterations in cardiovascular morphology.…”