Effects of amlodipine on glomerular filtration, growth, and injury in experimental hypertension.
The objective of this study was to determine whether the calcium antagonist amlodipine could slow the progression of chronic renal disease. We examined the effects of amlodipine on kidney structure and function in two experimental models of hypertension. In the first study, adult, male Munich Wistar rats underwent uninephrectomy and were given weekly injections of desoxycorticosterone and 1% saline for drinking. Rats ingested normal chow or chow containing amlodipine for 8 weeks. The drug reduced systemic blood pressure, but glomerular filtration rate, kidney weight, proteinuria, and morphological evidence of glomerular injury were not affected. In the second study, male spontaneously hypertensive rats underwent uninephrectomy at 5 weeks of age and were followed for 6 months, during which they received no therapy or amlodipine. The drug dose was determined in preliminary studies to be the highest dose not associated with marked growth retardation. Again, although systemic blood pressure was significantly reduced by amlodipine, proteinuria and the prevalence of glomerulosclerosis were similar in amlodipine-treated and control spontaneously hypertensive rats. Micropuncture studies revealed that glomerular pressure remained elevated in amlodipine-treated spontaneously hypertensive rats. Kidney weight and glomerular volume were also similar in amlodipine-treated and control rats. Amlodipine also failed to inhibit platelet aggregation. Therefore, antihypertensive therapy with amlodipine fails to reduce glomerular pressure in spontaneously hypertensive rats as well as glomerular size and injury in spontaneously hypertension rats and desoxycorticosterone-salt hypertension. Although other dihydropyridine calcium antagonists have been found to reduce experimental glomerular injury, these data suggest that amlodipine may not prevent hypertensive nephrosclerosis.
Dworkin
L D
LD
Department of Medicine, Brown University, Rhode Island Hospital, Providence 02903, USA.
Tolbert
E
E
Recht
P A
PA
Hersch
J C
JC
Feiner
H
H
Levin
R I
RI
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003900:Desoxycorticosterone; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006977:Hypertension, Renal / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011507:Proteinuria; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D017311:Amlodipine; D003900:Desoxycorticosterone