An ontogenic study of renal tissue kallikrein in Okamoto spontaneously hypertensive rats: comparisons with human hypertensive nephropathy.
Urinary excretion of tissue kallikrein is reduced in essential hypertension. Although a similar finding has been reported in spontaneously hypertensive rats (SHR), only a few studies have been concerned with the amount of enzyme within the kidney both at the time of onset and during progression of the hypertension. We have performed an ontogenic study on the renal parenchymal values and immunoreactivity of tissue kallikrein in Okamoto SHR aged 4-78 weeks. Additionally, these two parameters were analysed in human biopsies taken from patients with hypertensive nephropathy. The enzymatic activity of renal tissue kallikrein (active and total; specifically antagonized by anti-tissue kallikrein antibodies), increased from 4 to 52 weeks in SHR when compared to normotensive Wistar Kyoto (WKY) rats; this increase was associated with a significant increase in blood pressure. In contrast, 78 weeks SHR and human biopsy tissue showed a substantial reduction in tissue kallikrein values. Also, both renal tissues showed a reduction in immunoreactivity in the cells of the connecting tubules that specifically store the enzyme. In advanced hypertension the observed reduction in tissue kallikrein was probably secondary to a loss of distal tubular mass, as a result of tubular atrophy and fibrosis. The greater values for renal tissue kallikrein in the kidney and reported reduced urinary excretion during the early phases of spontaneous hypertension may be explained by a primary defect in the mechanisms that regulate release of tissue kallikrein from the connecting tubule cells.
Figueroa
C D
CD
Department of Pharmacology, Medical School, University of Bristol, U.K.
Bhoola
K D
KD
MacIver
A G
AG
Mackenzie
J C
JC
D000818:Animals; D001794:Blood Pressure; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007150:Immunohistochemistry; D007610:Kallikreins / Q000032:analysis / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D007610:Kallikreins