TY - JOUR
T1 - Effects of early carvedilol treatment and withdrawal on the development of hypertension and renal vascular narrowing
AU - Kett, Michelle M.
AU - Denton, Kate M.
AU - Boesen, Erika I.
AU - Anderson, Warwick P.
N1 - Funding Information:
Supported by a grant from GlaxoSmithKline and an NHMRC project grant (grant 124404), and by a Monash University Research Fund Fellowship (to MMK).
PY - 2004/2
Y1 - 2004/2
N2 - 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 At 12 weeks of age, rats from each group either underwent experimentation or had treatment withdrawn and were studied at 20 weeks.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.
AB - 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.
KW - Hypertension
KW - Sympathetic nervous system
KW - Vascular remodeling
KW - α -adrenoceptor
KW - β-adrenoceptor
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U2 - 10.1016/j.amjhyper.2003.09.013
DO - 10.1016/j.amjhyper.2003.09.013
M3 - Article
C2 - 14751659
AN - SCOPUS:1642452755
SN - 0895-7061
VL - 17
SP - 161
EP - 166
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 2
ER -