Effects of enalapril and clonidine on glomerular structure, function, and atrial natriuretic peptide receptors in SHHF/Mcc-cp rats.
Seven-month-old, lean male SHHF/Mcc-cp rats, a model of spontaneous hypertension, progressive renal dysfunction, and congestive heart failure (CHF), were treated with either clonidine (CL) or enalapril (EN) or received no treatment (CON) for 20 weeks. CL significantly decreased systolic blood pressure (SBP), kidney weights, and severity of renal lesions as compared with untreated CON. EN produced a decrease in SBP comparable to that in CL. Kidney weights and severity of renal histologic changes in the EN group were intermediate between those of the CL and CON groups. Despite similar plasma atrial natriuretic peptide (ANP) concentrations, CL treatment resulted in a significant increase in the density of guanylate cyclase-linked glomerular ANP receptors, whereas EN treatment resulted in a significant decrease in the total number of ANP receptors and in the number of nonguanylate cyclase-linked receptors and an increase in overall binding affinity. These findings demonstrate that antihypertensive agents will slow progression of renal injury in SHHF/Mcc-cp rats and that CL is more effective than EN in alleviating progressive kidney damage in this model. Furthermore, different classes of antihypertensive drugs may alter the density or ratio of biologically active and clearance ANP receptor sites in the glomerulus.
Radin
M J
MJ
Department of Veterinary Pathobiology, Ohio State University, Columbus.
Jenkins
J E
JE
McCune
S A
SA
Jurin
R R
RR
Hamlin
R L
RL
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001665:Binding Sites; D003000:Clonidine / Q000494:pharmacology*; D006152:Cyclic GMP / Q000652:urine; D004656:Enalapril / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D006984:Hypertrophy / Q000139:chemically induced; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000502:physiology
D011956:Receptors, Cell Surface; D004656:Enalapril; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D003000:Clonidine