BACKGROUND: Renal kallikrein has been linked with inheritance of arterial hypertension and with sensitivity to drug nephrotoxicity. Identification of a cause--effect relationship between low kallikrein and intermediate phenotypes has been hampered by the lack of adequate animal models. METHODS: Kallikrein was measured in tissues obtained from rats inbred for low urinary kallikrein excretion (LKR) and wild-type controls. Blood pressure and indices of myocardial contractility were recorded via an intraventricular cannula connected to a transducer. The functional relevance of endogenous angiotensin II (Ang II) in LKR was explored by determining the effect of Ang II subtype 1 (AT(1)) receptor blockade on glomerular filtration rate, renal blood flow, and urinary sodium excretion. In addition, sensitivity to gentamycin-induced nephrotoxicity was evaluated. RESULTS: Kallikrein activity was reduced by 60% in the kidney of LKR (P < 0.01), whereas it was increased in the heart (P < 0.05) and was unaltered in the pancreas, liver, and salivary glands. Heart rate and myocardial contractility were reduced, and the mean blood pressure (MBP) was increased in LKR as compared with controls (P < 0.05). LKR exhibited polydipsia, polyuria, glomerular hyperfiltration, and reduced fractional sodium excretion under basal conditions and impaired renal vasodilation in response to volume expansion. These functional alterations were significantly attenuated by AT(1) receptor blockade. Gentamycin reduced the glomerular filtration rate in LKR, but not in controls. CONCLUSIONS: In LKR, unopposed activity of Ang II appears to be responsible for increased glomerular hydrostatic pressure and augmented tubular reabsorption. Balance between the kallikrein-kinin and renin-angiotensin systems is essential for normal renal function.
BACKGROUND: Renal kallikrein has been linked with inheritance of arterial hypertension and with sensitivity to drug nephrotoxicity. Identification of a cause--effect relationship between low kallikrein and intermediate phenotypes has been hampered by the lack of adequate animal models. METHODS: Kallikrein was measured in tissues obtained from rats inbred for low urinary kallikrein excretion (LKR) and wild-type controls. Blood pressure and indices of myocardial contractility were recorded via an intraventricular cannula connected to a transducer. The functional relevance of endogenous angiotensin II (Ang II) in LKR was explored by determining the effect of Ang II subtype 1 (AT(1)) receptor blockade on glomerular filtration rate, renal blood flow, and urinary sodium excretion. In addition, sensitivity to gentamycin-induced nephrotoxicity was evaluated. RESULTS: Kallikrein activity was reduced by 60% in the kidney of LKR (P < 0.01), whereas it was increased in the heart (P < 0.05) and was unaltered in the pancreas, liver, and salivary glands. Heart rate and myocardial contractility were reduced, and the mean blood pressure (MBP) was increased in LKR as compared with controls (P < 0.05). LKR exhibited polydipsia, polyuria, glomerular hyperfiltration, and reduced fractional sodium excretion under basal conditions and impaired renal vasodilation in response to volume expansion. These functional alterations were significantly attenuated by AT(1) receptor blockade. Gentamycin reduced the glomerular filtration rate in LKR, but not in controls. CONCLUSIONS: In LKR, unopposed activity of Ang II appears to be responsible for increased glomerular hydrostatic pressure and augmented tubular reabsorption. Balance between the kallikrein-kinin and renin-angiotensin systems is essential for normal renal function.
Authors: Carlos P Vio; Mariana Quiroz-Munoz; Catherina A Cuevas; Carlos Cespedes; Nicholas R Ferreri Journal: Am J Physiol Renal Physiol Date: 2012-05-23
Authors: Felipe Cabezas; Jonathan Lagos; Carlos Céspedes; Carlos P Vio; Miguel Bronfman; María-Paz Marzolo Journal: PLoS One Date: 2011-02-02 Impact factor: 3.240
Authors: Joshua C Kwekel; Varsha G Desai; Carrie L Moland; Vikrant Vijay; James C Fuscoe Journal: Biol Sex Differ Date: 2013-07-31 Impact factor: 5.027