Faculty Collaboration Database

Effect of calcium channel blockade on adrenergically induced renal vasoconstriction in rat models of renal impairment. Clin Exp Pharmacol Physiol 2009 May;36(5-6):501-8

Date

08/14/2009

Pubmed ID

19673932

DOI

10.1111/j.1440-1681.2008.05098.x

Scopus ID

2-s2.0-65349142430 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

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.

Author List

Khan AH, Sattar MA, Abdullah NA, Johns EJ

MESH terms used to index this publication - Major topics in bold

Amlodipine
Animals
Calcium Channel Blockers
Diabetic Nephropathies
Disease Models, Animal
Drug Evaluation, Preclinical
Glomerular Filtration Rate
Kidney
Kidney Diseases
Male
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Receptors, Adrenergic
Renal Circulation
Renal Insufficiency
Vasoconstriction
Vasodilator Agents