Thiazide diuretics enhance nocturnal blood pressure fall and reduce proteinuria in immunoglobulin A nephropathy treated with angiotensin II modulators

Uzu, Takashi; Harada, Tamaki; Namba, Tomoko; Yamamoto, Ryohei; Takahara, Ken; Yamauchi, Atsushi; Kimura, Genjiro

doi:10.1097/01.hjh.0000163156.37363.47

Cited by 42 publications

(41 citation statements)

References 27 publications

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“…These results are consistent with the fact that the combination of thiazide diuretics and RAS inhibitors has been used to lower blood pressure and limit target-organ damage. 43,44 We acknowledge a limitation that the indirect tail-cuff method used to determine SBP is not adequate for ruling out the possibility that the results could be attributable to differences in blood pressure between the different treatment groups. 45 We also acknowledge that the use of anesthetics ketamine and xylazine may have affected some of our results including measurements of the RAS, because those agents may stimulate sympathetic nervous system in the rats.…”

Section: Discussionmentioning

confidence: 99%

Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension

et al. 2011

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Although thiazide diuretics are commonly used to supplement angiotensin receptor blockers for treatment of hypertension, the mechanism underlying the therapeutic effects of this drug combination remains unclear. We investigated the antihypertensive and cardioprotective effects of combination therapy with losartan (LOS) and hydrochlorothiazide (HCTZ), in comparison with those of either drug alone, in Dahl salt-sensitive hypertensive rats. Rats fed a high-salt diet from 6 weeks of age were treated with LOS, HCTZ, both drugs (COMB) and vehicle from 6 to 11 weeks. The salt-induced increase in systolic blood pressure was attenuated moderately by LOS and to a greater extent by HCTZ and COMB. Left ventricular (LV) hypertrophy and fibrosis, diastolic dysfunction, as well as angiotensin-converting enzyme and angiotensin II type 1A (AT 1A ) receptor gene expression were attenuated similarly by LOS and HCTZ and more so by COMB. LOS downregulated expression of the AT 1A receptor gene, without affecting that of the AT 2 receptor gene, in the aorta. In contrast, neither HCTZ nor COMB affected aortic expression of the AT 1A receptor gene, but both markedly upregulated that of the AT 2 receptor gene. The salt-induced decrease in the plasma concentration of nitric oxide metabolites was attenuated substantially by LOS and abolished by both HCTZ and COMB. In conclusion, the combination of LOS and HCTZ attenuated hypertension, as well as LV remodeling and diastolic dysfunction, more effectively than did LOS or HCTZ alone in rats with salt-sensitive hypertension. Modulation of the cardiac and vascular renin-angiotensin system may have contributed to these beneficial effects of the drug combination.

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Section: Discussionmentioning

confidence: 99%

Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension

et al. 2011

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“…However, it is as yet unknown whether this narrowing of PP induced by dual blockade of the renin-angiotensin system will translate into a long-term reduction in microvascular complications. Several researchers have demonstrated that it is possible to restore the normal circadian BP pattern in 'non-dipper's with selective antihypertensive therapy directed towards an elevated night BP [37][38][39][40]. Interestingly, this approach has been reported to reduce 24 h albumin excretion rate in microalbuminuric patients with essential hypertension, thus suggesting an increased organoprotective effect of reestablishing the normal diurnal BP rhythm [39].…”

Section: Discussionmentioning

confidence: 99%

Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients

et al. 2009

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Aims/hypothesis We followed type 2 diabetic patients over a long period to evaluate the predictive value of ambulatory pulse pressure (PP) and decreased nocturnal BP reduction (non-dipping) for nephropathy progression. Methods Type 2 diabetic patients (n=112) were followed for an average of 9.5 (range 0.5-14.5) years. At baseline, all patients underwent 24 h ambulatory BP measurement. Urinary albumin excretion rate was evaluated by three urinary albumin:creatinine ratio measurements at baseline and follow-up. Results At baseline, patients who subsequently progressed to a more advanced nephropathy stage (n=35) had reduced diastolic night/day BP variation and higher 24 h systolic BP and PP values; they also had more advanced nephropathy and were more likely to smoke than those with no progression of nephropathy (n=77). In a Cox regression analysis, independent predictors of nephropathy progression were 24 h PP (p<0.01), diastolic night:day BP ratio (p=0.02) and smoking (p=0.02). The adjusted hazards ratio (95% CI) for each mmHg increment in 24 h PP was 1.04 (1.01-1.07), whereas the adjusted hazards ratio (95% CI) for each 1% increase in diastolic night:day BP ratio was 1.06 (1.01-1.11). Only one of 33 patients (3.0%) with both a diastolic night:day BP ratio and a 24 h PP below the median progressed, whereas 17 of 32 patients (53.1%) with both a diastolic night:day BP ratio and a 24 h PP equal to or above the median progressed to a more advanced nephropathy stage (p<0.001). Conclusions/interpretation Ambulatory PP, impaired nocturnal BP decline and smoking are strong, independent predictors of nephropathy progression in type 2 diabetic patients.

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“…22 Much as in our previous reports, 23 our present patients with high baseline ANP and BNP levels were likely to have a high night-time systolic BP level, which strengthens the previous findings that persistent intravascular volume Table 4. Association between the change of BP, haemostasis, biochemical, and cardiovascular parameters before and after eplerenone treatment (n = 20) expansion is an important cause of uncontrolled BP, 24 and particularly uncontrolled night-time BP levels, 25 in hypertensive patients treated with anti-hypertensive agents that included ACEIs and ARBs 26 ; eplerenone may represent a more reasonable approach in such cases. However, in the present study, no significant differences were found in body weight, serum potassium level, or serum uric acid level between before and after eplerenone treatment.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of eplerenone added to renin-angiotensin blockade in elderly hypertensive patients: the Jichi-Eplerenone Treatment (JET) study

Yano

Hoshide

Tamaki³

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Introduction:We assessed the additional effects of eplerenone to angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on 24-h blood pressure (BP) level, fibrinolytic activity, and cardiovascular protection in elderly (>60 years) hypertensive patients. Materials and methods:In total, 20 patients (mean age 74 years, 25% men), whose BP was uncontrolled despite the use of anti-hypertensive drugs including ACEIs or ARBs (average 2.4 drugs), received eplerenone once daily (mean 37.5 mg) for 24 weeks. Results: Eplerenone treatment significantly reduced mean 24-h systolic/diastolic BP levels (143/80 mmHg to 132/74 mmHg, both p < 0.002). The reduction of 24-h systolic BP levels, especially night-time BP, was significantly associated with the reduction of atrial natriuretic peptide and brain natriuretic peptide levels (all p < 0.05). Furthermore, after eplerenone treatment, the mean plasminogen activator inhibitor-1 antigen level was significantly reduced (35 ng/ml to 25 ng/ml, p < 0.05), and the median level of plasma procollagen type III aminoterminal peptide and the urinary albumin excretion rate were also significantly reduced (0.8 U/ml to 0.6 U/ml, p < 0.003 and 53 mg/g·Cr to 23 mg/g·Cr, p < 0.05, respectively). During the intervention, eplerenone treatment was well tolerated with no reports of hyperkalaemia or hypotension. Conclusions: Addition of eplerenone to ACEIs or ARBs in elderly hypertensive patients offers significant benefits in terms of 24-h BP levels, fibrinolysis, and cardiovascular protection. KeywordsEplerenone, plasminogen activator inhibitor-1, procollagen type III aminoterminal peptide, urinary albumin excretion, 24-h blood pressure

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Thiazide diuretics enhance nocturnal blood pressure fall and reduce proteinuria in immunoglobulin A nephropathy treated with angiotensin II modulators

Cited by 42 publications

References 27 publications

Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension

Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension

Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients

Efficacy of eplerenone added to renin-angiotensin blockade in elderly hypertensive patients: the Jichi-Eplerenone Treatment (JET) study

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