title: Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation.
abstract: To determine whether pharmacological control of blood pressure could affect the renal function and levels of atrial natriuretic polypeptide (ANP) in spontaneously hypertensive rats (SHR) with renal ablation, and to ascertain the benefits of antihypertensive drugs, we studied effects of oral administration of captopril (50 mg/kg/day), an inhibitor of angiotensin converting enzyme, benidipine (3 mg/kg/day) and nilvadipine (10 mg/kg/day), newly developed blockers of calcium channel, and indapamide (10 mg/kg/day) for 14 days on systolic blood pressure, serum creatinine, blood urea nitrogen, and plasma ANP concentration in SHR subjected to surgical removal of the left kidney and infarction of two-thirds of the right kidney (5/6 nephrectomy) a week before. Three weeks after the surgery, systolic blood pressure (mmHg) in the untreated group was 253 +/- 9 (n = 10), in the captopril group 156 +/- 9 (n = 7, p less than 0.05), in the benidipine group 197 +/- 9 (n = 7, p less than 0.05), in the nilvadipine group 146 +/- 9 (n = 7, p less than 0.05) and in the indapamide group 206 +/- 5 (n = 7, p less than 0.05). Serum creatinine (mg/100 ml) was lower in the captopril group (0.58 +/- 0.02, n = 7, p less than 0.05) and in the benidipine group (0.50 +/- 0.03, n = 7, p less than 0.05) but not in the nilvadipine group and in the indapamide group 3 weeks after 5/6 nephrectomy compared to the untreated group. Blood urea nitrogen was also lower in the captopril group and in the benidipine group but not in the nilvadipine group and in the indapamide group. Plasma ANP concentration was significantly reduced by the treatment with captopril and benidipine but not with nilvadipine and indapamide. These results suggest that the reduction of blood pressure by the inhibition of angiotensin converting enzyme with captopril has the potential to ameliorate renal function of the SHR with remnant kidney, a model of chronic renal failure with hypertension, associated with the decreased concentration of plasma ANP. However, it remains to be determined whether the reduction of blood pressure by calcium channel blockers may be involved in the delayed progression of renal failure in this model since there were disparate effects on renal function and plasma ANP concentration with these two calcium channel blockers.
authors.affiliation: Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yasujima
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Kanazawa
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Kohzuki
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: K
authors.initials: K
authors.lastname: Omata
authors.forename: K
authors.initials: K
authors.lastname: Tsunoda
authors.forename: K
authors.initials: K
authors.lastname: Kudo
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D007190:Indapamide / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009392:Nephrectomy; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012016:Reference Values
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C035100:nilvadipine; C061004:benidipine; D009320:Atrial Natriuretic Factor; D002216:Captopril; D007190:Indapamide; D009543:Nifedipine