BACKGROUND: The present study investigated the contribution of alpha1-adrenergic blockade to hypertension induced by long-term blockade of nitric oxide and chronic treatment with deoxycorticosterone acetate (DOCA), which produced a low renin model of hypertension. We studied the effects of chronic administration of prazosin, an alpha1-receptor antagonist, on blood pressure (BP), renal injury, and other variables in N(omega)-nitro-L-arginine methyl ester (L-NAME) and L-NAME+DOCA hypertensive rats. MATERIAL/ METHODS: The rats were divided into 6 groups: Control, DOCA, L-NAME, L-NAME+DOCA, L-NAME+ prazosin, and L-NAME+DOCA+prazosin. Tail systolic BP was measured twice a week. After a 6-week evolution, mean arterial pressure (MAP) was measured, along with selected metabolic, morphological and renal variables. RESULTS: The final MAP values were 105+/-1 for Control, 107+/-0.6 for DOCA, 153+/-3 for L-NAME, 175+/-2 for L-NAME+DOCA, 126+/-2 for L-NAME+prazosin and 127+/-5 for L-NAME+DOCA+prazosin. Proteinuria and hyaline arteriopathy were prevented in L-NAME+prazosin rats and markedly attenuated in the L-NAME+DOCA+prazosin group. Plasma urea and creatinine were significantly increased in the L-NAME+DOCA group, but not in the L-NAME+ DOCA+prazosin group as against controls. The DOCA and DOCA+L-NAME groups showed relative renal and cardiac hypertrophy, which was not observed in the DOCA+L-NAME+prazosin group. CONCLUSIONS: Alpha1-adrenergic tone plays an important role in the increased BP and renal injury of L-NAME hypertension. Our results also indicate that when PRA is suppressed by DOCA in L-NAME hypertension, the increased BP and renal injury are largely dependent on the alpha1-adrenergic tone.
BACKGROUND: The present study investigated the contribution of alpha1-adrenergic blockade to hypertension induced by long-term blockade of nitric oxide and chronic treatment with deoxycorticosterone acetate (DOCA), which produced a low renin model of hypertension. We studied the effects of chronic administration of prazosin, an alpha1-receptor antagonist, on blood pressure (BP), renal injury, and other variables in N(omega)-nitro-L-arginine methyl ester (L-NAME) and L-NAME+DOCAhypertensiverats. MATERIAL/ METHODS: The rats were divided into 6 groups: Control, DOCA, L-NAME, L-NAME+DOCA, L-NAME+ prazosin, and L-NAME+DOCA+prazosin. Tail systolic BP was measured twice a week. After a 6-week evolution, mean arterial pressure (MAP) was measured, along with selected metabolic, morphological and renal variables. RESULTS: The final MAP values were 105+/-1 for Control, 107+/-0.6 for DOCA, 153+/-3 for L-NAME, 175+/-2 for L-NAME+DOCA, 126+/-2 for L-NAME+prazosin and 127+/-5 for L-NAME+DOCA+prazosin. Proteinuria and hyaline arteriopathy were prevented in L-NAME+prazosinrats and markedly attenuated in the L-NAME+DOCA+prazosin group. Plasma urea and creatinine were significantly increased in the L-NAME+DOCA group, but not in the L-NAME+ DOCA+prazosin group as against controls. The DOCA and DOCA+L-NAME groups showed relative renal and cardiac hypertrophy, which was not observed in the DOCA+L-NAME+prazosin group. CONCLUSIONS: Alpha1-adrenergic tone plays an important role in the increased BP and renal injury of L-NAMEhypertension. Our results also indicate that when PRA is suppressed by DOCA in L-NAMEhypertension, the increased BP and renal injury are largely dependent on the alpha1-adrenergic tone.
Authors: M Archer; N Dogra; Z Dovey; T Ganta; H-S Jang; J A Khusid; A Lantz; M Mihalopoulos; J A Stockert; A Zahalka; L Björnebo; S Gaglani; M R Noh; S A Kaplan; R Mehrazin; K K Badani; P Wiklund; K Tsao; D J Lundon; N Mohamed; F Lucien; B Padanilam; M Gupta; A K Tewari; N Kyprianou Journal: Cell Commun Signal Date: 2021-07-20 Impact factor: 5.712