Effects of early carvedilol treatment and withdrawal on the development of hypertension and renal vascular narrowing

Abstract Background The aims of this study were to examine whether combined blockade of α1 and β-adrenoceptors with carvedilol postweaning affected the development of hypertension and renal vascular narrowing in spontaneously hypertensive rats (SHR), and whether these effects on pressure and renal vascular changes persisted after treatment withdrawal. Methods From 4 to 12 weeks of age male SHR were administered carvedilol in rat chow at 1.2 mg/g chow (low-dose) or 2.4 mg/g chow (high-dose), or were given normal chow. At 12 weeks of age, rats from each group either underwent experimentation or had treatment withdrawn and were studied at 20 weeks. On the experimental day, conscious mean arterial pressure (MAP) was measured and, as a functional test of renal vessel lumen characteristics, pressure–flow and pressure–glomerular filtration rate (pressure–GFR) relationships were determined in the maximally dilated kidney. Results At 12 weeks of age, SHR on low and high-dose carvedilol had significantly lower MAP than that of untreated SHR (137 ± 3, 134 ± 1, 152 ± 2 mm Hg, respectively; P< .001). The SHR treated with high-dose (but not low-dose) carvedilol demonstrated a steeper renal pressure–flow relationship (P< .001), and a leftward shifted (P< .01) and steeper (P< .001) pressure–GFR relationship compared with control SHR. Eight weeks after carvedilol withdrawal, there were no significant differences in MAP, pressure–flow, or pressure–GFR relationships between groups. Conclusions These results suggest that postweaning α1 and β-adrenoceptor blockade with high-dose carvedilol attenuated the development of hypertension and led to a preferential reduction in preglomerular resistance (increased lumen dimensions) independent of the effects on MAP. However, treatment of SHR from 4 to 12 weeks of age with high-dose carvedilol did not lead to persistent, long-term effects on arterial pressure or renal vascular narrowing after treatment withdrawal.