Key result
Simultaneous administration of temocapril and doxazosin significantly reduced systolic blood pressure to 163 mmHg compared to 265 mmHg in controls, and provided greater renoprotective effects than temocapril alone.
Why the study?
Does combined temocapril and doxazosin improve renoprotection compared to temocapril alone in spontaneously hypertensive rats with renal ablation?
Does combined temocapril and doxazosin improve renoprotection compared to temocapril alone in spontaneously hypertensive rats with renal ablation?
Absolute Event Rate: 163% vs 265%
p-value: p=<0.001
Combined ACE inhibition and alpha-1-adrenergic antagonism provides greater renoprotection than ACE inhibition alone in a hypertensive rat model of chronic kidney disease.
Extends preclinical support for combined ACE inhibition and alpha-blockade in hypertensive CKD models; leaves open translation to patients.
To assess the renal benefits of combined angiotensin-converting enzyme inhibition and alpha(1)-adrenergic antagonism, we studied the antihypertensive and renoprotective effects of temocapril (TMP) alone and in combination with doxazosin (DOX) in spontaneously hypertensive rats (SHR)/Izumo rats with renal ablation. Five-Sixths-nephrectomized rats were assigned to receive TMP (10 mg/kg/day) (TMP group), TMP plus DOX (2 mg/kg/day) (TMP+DOX group), or vehicle (control group) orally for 12 weeks. Both systolic blood pressure (SBP) and urinary excretion of albumin (UalbV) in the control group progressively increased during the experimental period and were significantly higher than in sham-operated rats. Treatment with either TMP or TMP plus DOX had similar antihypertensive effects in this rat model. Twelve weeks after initiation of treatment, the SBP values in the control, TMP, and TMP+DOX groups were 265+/-8, 157+/-4, and 163+/-3 mmHg, respectively, in comparison with 233+/-4 mmHg in sham-operated rats (p<0.0001 control vs. sham, p<0.001 TMP vs. control, p<0.001 TMP+DOX vs. control). UalbV, serum creatinine (Scr), blood urea nitrogen (BUN), and heart weight/body weight (HW/BW) ratio were significantly lower in the TMP and TMP+DOX groups than in the control group (UalbV: p<0.05; Scr: p<0.01; [BUN, HW/BW ratio]: p<0.0001; and [UalbV, Scr, BUN, HW/BW ratio]: p<0.0001 vs. control, respectively). The index of glomerular sclerosis (IGS) and relative interstitial volume (RIV) were significantly lower in the TMP+DOX group than in the control group (IGS: p<0.05; RIV: p<0.01). Especially, UalbV, IGS, and RIV were significantly better in the TMP+DOX group than in the TMP group ([IGS, RIV]: p<0.05; UalbV: p<0.01). These results suggest that simultaneous administration of TMP and DOX provides greater renoprotective effects than administration of TMP alone.
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Kanazawa et al. (2004) studied Chronic renal failure and hypertension (n=34). Temocapril plus doxazosin vs. Vehicle (control) and Temocapril alone was evaluated on Systolic blood pressure at 12 weeks (p=<0.001). Simultaneous administration of temocapril and doxazosin significantly reduced systolic blood pressure to 163 mmHg compared to 265 mmHg in controls, and provided greater renoprotective effects than temocapril alone.
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