Renal Protective Effects of Amlodipine on Partially Nephrectomized Spontaneously Hypertensive Rats Fed a High-Salt Diet

Kanno, Yoshihiko; Suzuki, Hiromichi; Okada, Hirokazu; Saruta, Takao

doi:10.1097/00005344-199423030-00018

Cited by 7 publications

(10 citation statements)

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“…Both antihypertensive treatments in the present study reduced the levels of proteinuria, in agreement with previous studies (20,21). The mechanism of the effects on reducing proteinuria of antihypertensives (ACE inhibitors, CCBs, and α-blocker) (6,22) were explained mainly by reducing blood pressure, but both ACE inhibitors and CCBs are reported that they have the effects which are not due to lowering the blood pressure (2,3).…”

Section: Discussionsupporting

confidence: 92%

The Effects of Antihypertensive Agents on the Survival Rate of Polycystic Kideney Disease in Han: SPRD Rats.

et al. 2002

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder in humans. Hypertension is one of the major complications, and its control might affect the renal survival and disease mortality. Suitable antihypertensive agents have been discussed based on clinical and animal studies, but no definitive conclusion has been reached. Generally, therefore, all antihypertensives are indiscriminately treated as if providing the same level of blood pressure control. In this study, the blood pressure control of two antihypertensives was investigated using a rat model of ADPKD in humans. Twenty-four male Hannover-Sprague Dawley (Han:SPRD) rats were divided into three groups: a group receiving amlodipine (6 mg/day), a group receiving benazepril (6 mg/day) and an untreated control group. Blood pressure, body weight, and urinary protein excretion were regularly measured up to week 52. Amlodipine and benazepril significantly decreased blood pressure and urinary protein excretion to the same degree. Moreover, a remarkably prolonged survival rate was observed in both groups (at week 52, the survival rate was 25% in controls, 50% in the amlodipine group, and 50% in the benazepril group). Examination at autopsy revealed that enlarged cysts were prevalent in the renal tissue of both experimental all three groups, suggesting that the cystic disease had reached the end-stage in all the animals. In conclusion, both amlodipine and benazepril significantly improved blood pressure control, urinary protein excretion, and survival rate, possibly due to their enhancement of renal survival.

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Section: Discussionsupporting

confidence: 92%

The Effects of Antihypertensive Agents on the Survival Rate of Polycystic Kideney Disease in Han: SPRD Rats.

et al. 2002

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“…In addition, calcium antagonists may reduce glomerular hypertrophy, resulting in a decrease in capillary wall tension (25). Thus, our laboratory reported that amlodipine preserved renal function in subtotally nephrectomized SHR (26). Conversely, in patients with diabetic nephropathy, nifedipine has been reported to accelerate the progression of renal injury (20,27), suggesting that selective afferent arteriolar vasodilation could exacerbate intraglomerular hypertension.…”

Section: Discussionmentioning

confidence: 95%

Disparate Effects of Calcium Antagonists on Renal Microcirculation.

et al. 1996

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Although calcium antagonists reduce systemic blood pressure, the effects of calcium antagonists on renal preglomerular and postglomerular microcirculation have been suggested to differ. In the present study we examined the vasodilator action of dihydropyridine-type calcium antagonists, including nifedipine, nicardipine, amlodipine, and efonidipine, on afferent and efferent arterioles during angiotensin II (A-II)- and norepinephrine (NE)-induced renal vasoconstriction. Isolated perfused hydronephrotic kidneys were used to directly visualize renal microcirculatory response to calcium antagonists. Both A-II and NE caused marked vasoconstriction of afferent (A-II, 27 +/- 2% decrement; NE, 28 +/- 2% decrement) and efferent arterioles (A-II, 25 +/- 4% decrement; NE, 22 +/- 2% decrement). The subsequent addition of nifedipine, nicardipine, and amlodipine reversed the afferent arteriolar vasoconstriction in a dose-dependent manner, and elicited complete vasodilation at 10(-6) M. In contrast, efferent arteriolar vasoconstriction was relatively refractory to the dilator action of these calcium antagonists; maximal dilation observed at 10(-6) M was 21 +/- 1% (A-II) and 22 +/- 3% (NE) for nifedipine, 25 +/- 3% (A-II) and 20 +/- 6% (NE) for nicardipine, and 39 +/- 6% (A-II) and 37 +/- 3% (NE) for amlodipine. In striking contrast, efonidipine dilated not only afferent arterioles, but also efferent arterioles in a dose-dependent manner. At 10(-6) M, efonidipine completely inhibited the afferent (A-II, 89 +/- 7% reversal; NE, 99 +/- 8% reversal) and efferent arteriolar vasoconstriction (A-II, 93 +/- 4% reversal; NE, 87 +/- 9% reversal). These findings clearly demonstrate that calcium antagonists dilate the afferent arteriole. Unlike the effects on the afferent arteriole, efferent arteriolar responsiveness to calcium antagonists differ, depending on the type of calcium antagonist. The efonidipine-induced efferent arteriolar vasodilation is probably not related to voltageoperated calcium channels, and may act, in concert with blood pressure lowering effect, to ameliorate glomerular capillary hypertension.

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“…По результатам ряда исследований, антигипертензивное действие АК сопровождается уменьшением ст. выраженности клубочковой гипертензии и способствует нефропротекции [27][28][29][30]. По другим данным, преимущественное действие этих препаратов на афферентные артериолы может приводить к клубочковой гипертензии и прогрессированию патологии почек [31][32][33][34].…”

Section: Discussionunclassified

Treatment of proteinuria with lercanidipine associated with reninangiotensin axis-blocking drugs

Robles

Romero

Винуэза

et al. 2011

Cardiovasc Ther Prev

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Aim. Most calcium antagonists do not seem to reduce microalbuminuria or proteinuria. We have tried to assess the antiproteinuric effect of a calcium channel blocker, lercanidipine, in patients previously treated with ACE inhibitors or angiotensin receptor blockers. Design and methods. The study included 68 proteinuric (>500 mg/day) patients (age 63,1±12,9 years, 69,1 % males and 30,9 % females). All patients were receiving ACE inhibitors (51,4 %) or angiotensin II receptor blockers (48,6 %) therapy but had higher blood pressure (BP) than recommended for proteinuric patients (<130/80 mm Hg). Patients were clinically evaluated one, three, and six months after starting treatment with lercanidipine (20 mg/day). Samples for urine and blood examination were taken during the examination. When needed, a third drug was added to treatment. Creatinine clearance was measured using 24 h urine collection. Results. BP significantly decreased from 152±15/86±11 mm Hg to 135±12/77±10 mm Hg at six months of follow-up (p<0,001). After six months of treatment, the percentage of normalized patients (BP <130/80 mm Hg) was 42,5 %, and the proportion of patients whose BP was below 140/90 mm Hg was 58,8 %. Plasmatic creatinine did not change nor did creatinine clearance. Plasmatic cholesterol also decreased from 210±48 to 192±34 mg/dL (p<0,001), as did plasma triglycerides (from 151±77 to 134±72 mg/dL, p=0,022). Basal proteinuria was 1,63±1,34 g/day; it was significantly (p<0,001) reduced by 23 % at the first month, 37 % at three months, and 33 % at the last visit.Conclusion. Lercanidipine at 20 mg dose, associated with renin-angiotensin axis-blocking drugs, showed a high antihypertensive and antiproteinuric effect. This antiproteinuric effect seems to be dose-dependent as compared with previous reports and proportionally higher than blood pressure reduction.

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Renal Protective Effects of Amlodipine on Partially Nephrectomized Spontaneously Hypertensive Rats Fed a High-Salt Diet

Cited by 7 publications

References 0 publications

The Effects of Antihypertensive Agents on the Survival Rate of Polycystic Kideney Disease in Han: SPRD Rats.

The Effects of Antihypertensive Agents on the Survival Rate of Polycystic Kideney Disease in Han: SPRD Rats.

Disparate Effects of Calcium Antagonists on Renal Microcirculation.

Treatment of proteinuria with lercanidipine associated with reninangiotensin axis-blocking drugs

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