An evaluation of the renal protective effect of manidipine in the uninephrectomized spontaneously hypertensive rat.
The effects of calcium antagonism on the development and progression of renal disease are controversial. To address this problem, studies were performed on young, uninephrectomized spontaneously hypertensive rats (SHRs) with the dihydropyridine calcium antagonist, manidipine, to assess its effect on the early pathogenesis of focal glomerulosclerosis. Male SHRs underwent uninephrectomy at age 10 to 11 weeks and were subsequently assigned to no treatment (control), a predetermined subvasodepressor (low) dose of manidipine (2.5 mg/kg body weight), or a predetermined antihypertensive (high) dose of manidipine (20 mg/kg body weight). All animals received a diet containing 0.4% sodium and 23% protein. Serial determinations of body weight, systolic tail cuff pressure, and 24-hour urinary excretion of creatinine, sodium, and protein (UprotV) were made at 1- to 6-week intervals, for a total treatment period of 12 weeks. In final experiments plasma was obtained for creatinine, angiotensin I, and angiotensin II determinations, and renal tissue was harvested for histologic and morphometric analysis. Compared with the untreated control, low-dose manidipine therapy had no effect on body weight, systolic blood pressure, creatinine clearance, UprotV, renal histologic findings, glomerular volume, or plasma angiotensin I or II concentrations. In contrast, high-dose manidipine therapy decreased systolic blood pressure from 194 +/- 3 to 160 +/- 4 mm Hg (p < 0.01). Creatinine clearance and UprotV were unchanged. Although body weight was not different, kidney weight was higher. However, mean glomerular volume was lower. More importantly, the prevalence of mesangial expansion with proliferation was lower: 6.7% (control) versus 2.8% (high-dose manidipine) (p < 0.01). Finally, plasma angiotensin I and angiotensin II concentrations did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)
Reams
G P
GP
Hypertension Research Center, University of Missouri, Columbia 65212.
Villarreal
D
D
Wu
Z
Z
Wang
X
X
Luger
A M
AM
Bauer
J H
JH
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000627:therapeutic use*; D005920:Glomerular Mesangium / Q000033:anatomy & histology / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009392:Nephrectomy; D009578:Nitrobenzenes; D010879:Piperazines; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D011918:Rats, Inbred SHR
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D000804:Angiotensin II; C054218:manidipine