To assess the renal benefits of combined
angiotensin-converting enzyme inhibition and
calcium antagonism, we studied the
antihypertensive and renoprotective effects of
temocapril (
TMP) alone or in combination with
azelnidipine (AZN) in a spontaneously hypertensive rat (SHR) remnant kidney model of
chronic renal failure. Male 5/6-nephrectomized SHR/Izumo rats were randomly assigned to receive vehicle (control group),
TMP (
TMP group; 10 mg x kg(-1) x day(-1)), AZN (AZN group; 3 mg x kg(-1) x day(-1)), or both (TMP+AZN group) orally for 12 weeks. Systolic blood pressure (SBP) and urinary excretion of
albumin (UalbV) were measured every 2 weeks. At the end of the experiment, serum
creatinine (Scr), heart weight (HW), and blood
urea nitrogen (BUN) levels were measured and the remnant kidneys were examined to determine the index of glomerular
sclerosis (IGS). SBP and UalbV in the control group increased progressively throughout the experimental period.
TMP, AZN, and TMP+AZN blocked the development of
hypertension. TMP+AZN did not enhance the
antihypertensive effects of either
TMP or AZN used singly.
TMP, AZN, and TMP+AZN all significantly decreased the UalbV, Scr, BUN, and HW/
body weight (BW) ratio. The level of UalbV and the HW/BW ratio in the TMP+AZN group were significantly lower than those in the
TMP and AZN groups, and the level of Scr in the TMP+AZN group was significantly lower than that in the
TMP group.
TMP, AZN, and TMP+AZN all significantly protected against an increase in the IGS. The IGS in the TMP+AZN group was significantly lower than that in the
TMP and AZN groups. These results indicate that both
TMP and AZN have
antihypertensive and renoprotective effects in this model. They also suggest that simultaneous administration of
TMP and AZN provides greater renoprotective effects than
TMP alone.