Protective effects of valsartan and benazeprilat in salt-loaded stroke-prone spontaneously hypertensive rats.
These experiments examined the effectiveness of chronic blockade of the renin angiotensin system with either valsartan or benazeprilat on survival, blood pressure and end-organ damage in salt-loaded stroke-prone SHR. Valsartan or benazeprilat given continuously by subcutaneous osmotic minipump beginning at 10.5 weeks of age lowered blood pressure, as determined by radiotelemetry, prevented proteinuria, prolonged survival and decreased the severity of histopathological changes in the heart and kidney. These results indicate that angiotensin receptor blockade affords a similar degree of protection as inhibition of angiotensin converting enzyme in salt-loaded stroke-prone SHR. Furthermore, our results are consistent with a primary contribution of angiotensin II to the maintenance of blood pressure and support a principal role for angiotensin II-dependent mechanisms in the development of end-organ damage in the salt-loaded stroke-prone SHR.
Webb
R L
RL
Metabolic and Cardiovascular Diseases, Novartis Pharmaceuticals Corporation, Summit, New Jersey 07901-1398, USA.
Barclay
B W
BW
Navarrete
A E
AE
Wosu
N J
NJ
Sahota
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007260:Infusion Pumps; D007668:Kidney / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D013777:Tetrazoles; D012965:Sodium Chloride; D000068756:Valsartan; D012083:Renin; D014633:Valine; C052133:benazeprilat