Regulatory effects of salt diet on renal renin-angiotensin-aldosterone, and kallikrein-kinin systems.
The interaction of the renin-angiotensin-aldosterone system (RAAS) and the kallikrein-kinin system (KKS) was investigated in rats fed on a low, normal, and high-salt diet for 2 weeks. At the beginning of the second week, either a B2-receptor antagonist (icatibant), or an AT1-receptor antagonist (losartan), or an aldosterone receptor antagonist (spironolactone) was applied via osmotic pump delivering a constant amount of drug for 7 days. The urinary bradykinin (BK) levels corresponded with increasing NaCl diet and the activity of urinary kallikrein. However, in agreement with other investigators we found a down-regulation of the renal kallikrein gene expression in response to an increasing NaCl diet. Renal kinins are able to stimulate the renal kallikrein expression as well as the renal excretion of active kallikrein via the B2-receptor. The release of renal kallikrein is also mediated by angiotensin II (AngII). After high-salt diet the blood pressure was significantly increased. Losartan and spironolactone were not effective in reducing this increase, as AngII and aldosterone should be low during high-salt diet. However, low-salt diet also yielded an increase in blood pressure, which, however, could be abolished following losartan infusion. The data suggest that the expression of renal kallikrein mRNA is mainly regulated by dietary salt intake. However, kinins are able to stimulate the kallikrein gene expression, as well as the renal kallikrein release. Angll mediates only a stimulatory effect on the urinary kallikrein release. In contrast to the general belief, our data support the opinion that low-salt diet is able to mediate an increase in blood pressure, as the RAAS is stimulated in response to a marked salt deficiency.
Hettinger
Ute
U
Department of Pharmaceutical Pharmacology, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 366, 69 120 Heidelberg, Germany.
Lukasova
Martina
M
Lewicka
Sabina
S
Hilgenfeldt
Ulrich
U
D000818:Animals; D001920:Bradykinin / Q000652:urine; D016234:Kallikrein-Kinin System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000494:pharmacology; D020840:Tissue Kallikreins / Q000096:biosynthesis / Q000652:urine
D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D020840:Tissue Kallikreins; D001920:Bradykinin