Persistent effects on blood pressure and renal haemodynamics following chronic angiotensin converting enzyme inhibition with perindopril.
Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats aged 4 and 16 weeks were given an acute oral dose of either Perindopril (3 mg/kg) or vehicle. Direct blood pressure (BP), glomerular filtration rate (GFR) and renal blood flow (RBF) were measured, and renal vascular resistance (RVR) calculated. GFR and RBF were lower in vehicle-treated SHR than WKY at 4 weeks of age, but were not different at 16 weeks. Acute Perindopril increased GFR and RBF and reduced RVR in both strains at both 4 and 16 weeks. Total body sodium, sodium intake and blood pressure were measured in SHR and WKY from 1 to 28 weeks of age. Rats of both strains were treated daily between 4 and 16 weeks of age with either Perindopril (3 mg/kg per day) or vehicle. Chronic Perindopril treatment prevented the development of hypertension in the SHR. From 16 to 28 weeks of age, after stopping Perindopril, BP rose slowly in SHR, but remained lower than vehicle-treated SHR. No changes in total body sodium occurred during Perindopril treatment. GFR and RBF were measured in SHR and WKY chronically treated with either Perindopril or vehicle, 3 days or 12 weeks after stopping treatment. In WKY, GFR and RBF were not different between Perindopril-treated and untreated rats at either measurement. In SHR, GFR and RBF remained significantly higher in rats previously treated with Perindopril at both ages. These findings suggest that renal haemodynamic abnormalities may be important in the initiation of hypertension in the SHR. These renal circulatory abnormalities and the hypertension of the SHR depend, at least in part, on intact converting enzyme activity, yet appear to be independent of abnormalities of total body sodium. At a later age, hypertension seems to develop independently of renal vascular abnormalities.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D012964:Sodium; D020913:Perindopril