Role of the renal kallikrein-kinin system in the development of salt-sensitive hypertension.
The role of the renal kallikrein-kinin system in the development of salt-sensitive hypertension was studied using mutant kininogen-deficient Brown-Norway Katholiek (BN-Ka) rats, which generate no kinin in their urine, and other hypertensive rat models. It was found that ingestion of a low sodium diet or infusion of NaCl in doses slightly above 0.15 M caused hypertension and sodium accumulation in erythrocytes and the cerebrospinal fluid of kininogen-deficient BN-Ka rats. Development of hypertension in the deoxycorticosterone-acetate-salt model was completely prevented by administration of a newly discovered inhibitor, ebelactone B, of carboxypeptidase Y-like exopeptidase (an urinary kininase). The urinary kallikrein excretion of spontaneously hypertensive rats was lower than that of Wistar Kyoto rats at 4 weeks of age and did not increase by administration of furosemide, a diuretic agent, although approximately 50% of the diuretic action of this agent was dependent upon the renal kallikrein-kinin system in normal rats. In conclusion, the renal kallikrein-kinin system works as a safety valve for excess sodium intake.
Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
M
M
Katori
M
M
Majima
I
I
Hayashi
T
T
Fujita
M
M
Yamanaka
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000503:physiopathology*; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents