Chronic treatment with losartan and carvedilol differentially modulates renal vascular responses to sympathomimetics compared to treatment with individual agents in normal Wistar Kyoto and spontaneously hypertensive rats.
This study set out to investigate the impact of chronic cumulative blockade of angiotensin II and adrenoceptors in WKY and SHR and to explore how the renovascular responses to adrenergic and angiotensin II receptor agonists may be interdependent. Rats were treated with either losartan, carvedilol or losartan+carvedilol for 7 days and on day eight, animals were pentobarbitone anaesthetized and prepared for renal haemodynamic study. Dose-response relationships were determined in terms of reduction/elevation in the magnitude of renal blood flow in response to intrarenal arterial injection of dopamine, phenylephrine and isoprenaline. Renal vascular responses were blunted in WKY and SHR treated with either losartan or carvedilol as compared to their untreated counterparts (P<0.05). In the combined treated rats, the vascular responses to isoprenaline and phenylephrine were restored to levels observed in the untreated rats, but the renal vasoconstrictor responses to dopamine decreased (P<0.05) in both WKY and SHR. There was a reduction of (P<0.05) in the magnitude of the isoprenaline induced renal vasodilation in all SHR as compared to WKY groups. The data obtained showed that the renal vascular action of dopamine, phenylephrine and isoprenaline depended on an intact renin-angiotensin system (RAS) in WKY and SHR. Treatment with losartan or carvedilol blunted the renal vasoconstrictor/vasodilator responses to sympathomimetics which was attenuated with the combined treatment. These observations using chronic blockade of adrenergic and angiotensin receptors demonstrated that there was a long standing interdependency between the RAS and sympathetic nervous system (SNS) in determining the responsiveness of the renal vasculature of normal and hypertensive rats.
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia. mdapharm78@yahoo.co.uk
Mohammed H
MH
Abdulla
Munavvar A
MA
Sattar
Nor A
NA
Abdullah
Md Abdul H
MA
Khan
H H
HH
Abdallah
Edward J
EJ
Johns
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000294:innervation; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow / Q000187:drug effects; D013566:Sympathomimetics / Q000494:pharmacology*; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002227:Carbazoles; D004338:Drug Combinations; D011412:Propanolamines; D013566:Sympathomimetics; D000077261:Carvedilol; D019808:Losartan