Effect of calcium channel blockade on adrenergically induced renal vasoconstriction in rat models of renal impairment.
1. Calcium channel blockade attenuates adrenergically induced renal vasoconstriction and the present study examined whether the magnitude of the supression was enhanced or blunted in rat models of renal failure or diabetes-induced glomerular hyperfiltration. 2. Male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were used that had either renal failure induced by cisplatin administration or early diabetic nephropathy (EDN) consequent to an injection of streptozotocin (STZ). After 7 days of cisplatin or 4 weeks of STZ, rats were anaesthetized and renal haemodynamic studies were performed. 3. Cisplatin-treated WKY rats and SHR exhibited reduced creatinine clearance (CCr) and increased fractional excretion of sodium (FE(Na)) and kidney index (all P < 0.05), along with tubular damage in the kidney, compared with non-treated rats. In the EDN model, there was marked albuminuria and increased FE(Na), kidney index and CCr (all P < 0.05) compared with non-diabetic nephropathy (NDN) rats. Amlodipine significantly (P < 0.05) and dose-dependently attenuated the magnitude of the neurally and adrenergically induced renal vasoconstriction in all experimental groups compared with their respective control groups (13-6 vs 9-5% in renal failure vs non-renal failure WKY rats; 26-15 vs 17-8% in renal failure vs non-renal failure SHR; 19-9 vs 14-5% in EDN vs NDN). 4. The data obtained demonstrate that not only does amlodipine blunt adrenergically induced renal vasoconstriction in normal rats, but that it also does so, and to a greater extent, in rats with either renal failure or hyperfiltration.
Khan
Abdul H
AH
Tulane Hypertension and Renal Center of Excellence, Tulane University, New Orleans, Louisianna, USA.
Sattar
Munavvar A
MA
Abdullah
Nor A
NA
Johns
Edward J
EJ
D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D007674:Kidney Diseases / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011941:Receptors, Adrenergic / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D051437:Renal Insufficiency / Q000139:chemically induced / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D011941:Receptors, Adrenergic; D014665:Vasodilator Agents; D017311:Amlodipine