Antihypertensive effects of cicletanine and renal protection in Dahl salt-sensitive rats.
We designed experiments to reveal the antihypertensive properties of cicletanine, a novel antihypertensive drug, in Dahl salt-sensitive (Dahl-S) rats. Cicletanine (39 mg/kg body weight per day for 6 weeks) ameliorated the development of hypertension in Dahl-S rats fed a high-salt (4% NaCl) diet. This blood pressure reduction was associated with a decrease in heart weight and vascular wall thickness. Moreover, urinary prostacyclin (PGl2) excretion was increased with cicletanine treatment, being inversely related to systolic blood pressure. Proteinuria and urinary excretion of n-acetyl-beta-D-glucosaminidase were decreased and glomerular filtration rate was increased with this treatment. Morphological investigation revealed an improvement in glomerulosclerosis, renal tubular damage and intrarenal arterial injury in the salt-induced hypertensive rats. In contrast, trichloromethiazide, which decreased blood pressure to the same extent as cicletanine, lowered urinary PGl2 excretion and generally did not ameliorate the deteriorated renal functions and morphological abnormalities. Thus, these data indicate that cicletanine ameliorates the development of hypertension in Dahl-S rats and protects the cardiovascular and renal systems against the injuries seen in the hypertension. The enhanced vasodepressor PGl2 synthesis probably participates, to some extent, in these beneficial properties of long-term cicletanine treatment.
Uehara
Y
Y
2nd Department of Medicine, University of Tokyo, Japan.
Numabe
A
A
Hirawa
N
N
Kawabata
Y
Y
Iwai
J
J
Ono
H
H
Matsuoka
H
H
Takabatake
Y
Y
Yagi
S
S
Sugimoto
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood / Q000494:pharmacology*; D015232:Dinoprostone / Q000652:urine; D004232:Diuretics / Q000097:blood / Q000494:pharmacology*; D015777:Eicosanoids / Q000652:urine; D011464:Epoprostenol / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D011725:Pyridines; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine; D012965:Sodium Chloride; D013928:Thromboxane A2 / Q000652:urine
D000959:Antihypertensive Agents; D004232:Diuretics; D015777:Eicosanoids; D011725:Pyridines; D012965:Sodium Chloride; D013928:Thromboxane A2; D012964:Sodium; C038068:cicletanine; D011464:Epoprostenol; D015232:Dinoprostone