Effect of angiotensin II type 1 receptor blocker, candesartan, and beta 1 adrenoceptor blocker, atenolol, on brain damage in ischemic stroke.
This work aims at studying the possible alteration of renal renin secretion after human ischemic stroke and correlating it to the post stroke neurological and renal function alterations using angiotensin II type 1(AT1) receptor blocker (ARB), candesartan, and beta 1 adrenoreceptor blocker atenolol, which inhibits renin secretion, in Wistar rats subjected to middle cerebral artery occlusion. Methods . This study comprised 21 patients with cerebral ischemic stroke. Seventeen normal persons were used for comparison. Recumbent and standing plasma renin activity (PRA), reflex plasma renin sensitivity, plasminogen activator inhibitor and creatinine clearance (Ccr) were estimated at admission and two weeks later. Moreover, 60 male Wistar rats were divided into two groups SHAM and ischemic. Each of the two groups was further subdivided into three subgroups, non-treated, atenolol treated, and candesartan treated. In all rats, mean arterial blood pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), heart rate (HR), neurobehavioral evaluation, Ccr, PRA, and infarct size were measured. Results . Together with the significant deterioration of the neurological score, focal cerebral ischemia in rats resulted in increased PRA and decreased glomerular filtration rate (GFR). In ischemic stroke patients, GFR was significantly decreased at admission and two weeks later, PRA increased at admission and two weeks later while plasma renin reflex secretion sensitivity had decreased significantly at admission relative to controls, but it increased significantly 2 weeks later. Atenolol caused significant improvement of the neurobehavioral score and renal function and decrease infarct size of rats subjected to focal cerebral ischemia whereas candesartan caused significant improvement of the neurobehavioral score and decreased infarct size with no significant change in GFR. Neither atenolol nor candesartan caused significant change in MAP, SBP, DBP, PP and HR Conclusion . (1) Ischemic stroke seems to be associated with a postischemic increase of the plasma renin secretion, which may increase the infarct size in the brain and may induce acute renal insufficiency. (2) This study confirms that Atenolol and ARBs could benefit ischemic stroke patients without altering blood pressure.
Department of Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
M Ahdy A
MA
Saad
Amr M
AM
Abbas
V
V
Boshra
M
M
Elkhateeb
I Abd
IA
El Aal
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds; D002545:Brain Ischemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D002534:Hypoxia, Brain / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D015849:Plasminogen Inactivators / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D015849:Plasminogen Inactivators; D013777:Tetrazoles; D001262:Atenolol; D003404:Creatinine; D012083:Renin; C081643:candesartan