Nipradilol inhibits DNA synthesis by regulating nitric oxide synthesis in cultured rat mesangial cells

Nitta, Kosaku; Tsutsui, Takaaki; Uchida, Keiko; Eto, Yoko; Natori, Kyoko; Honda, Kazuho; Yumura, Wako; Nihei, Hiroshi

doi:10.1016/s0014-2999(97)01613-0

Cited by 7 publications

(7 citation statements)

References 6 publications

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“…L -Arginine and NO donors have been shown to have renoprotective effects in the remnant kidney model [18, 19, 37]. Nipradilol and isosorbide dinitrate have been shown to inhibit mesangial cells proliferation through the activation of soluble guanylate cyclase [23, 24, 38]. Furthermore, we observed a significant negative correlation between the glomerulosclerosis index or proteinuria and the urinary excretions of NO metabolites and cyclic GMP.…”

Section: Discussionmentioning

confidence: 51%

“…In the present study, we selected a novel vasodilating β-blocker with a nitroxy (ONO 2 ) group [20, 21], which has been reported to increase NO in aortic endothelial cells by in vitro, about 50% as an NO donor, and the rest as a result of eNOS upregulation [22], as well as to inhibit rat mesangial mitogenesis [23, 24]. For the purpose of estimating the role of an ONO 2 group, the comparison with propranolol, a typical nonselective β-blocker without an ONO 2 group, was made.…”

Section: Introductionmentioning

confidence: 99%

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A Nitric Oxide-Generating Beta-Blocking Agent Prevents Renal Injury in the Rat Remnant Kidney Model

Takamitsu¹,

Nakanishi²,

Nishihara³

et al. 2003

Nephron Physiol

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Background: The L-arginine-nitric oxide (NO) pathway plays an important role in the modulation of glomerular disease. We investigated whether β-blocking agents, with and without an NO-generating function, had renoprotective effects in the 5/6 nephrectomized rats (Nx), an animal model of glomerulosclerosis. Methods: Nipradilol, a β-blocker with an ONO₂ group (5, 10 or 15 mg/kg/day) and propranolol, a β-blocker without this group (50 mg/kg/day) were administered for 12 weeks to Nx together with and without nitro-L-arginine methyl ester (L-NAME). We evaluated the effects of both drugs on proteinuria, hypertension, renal function, glomerulosclerosis and urinary excretion of NO metabolites (U_NOx) and cyclic GMP (U_cGMP). Results: Both drugs similarly attenuated the elevated blood pressure in Nx. However, nipradilol, at doses of 10 and 15 mg/kg/day, significantly decreased proteinuria and glomerulosclerosis, while propranolol did not. Nx showed reduced U_NOx in comparison with the sham-operated rats. Nipradilol increased U_NOx and U_cGMP significantly and in a dose- dependent manner, whereas propranolol reduced them to levels lower than those in Nx. Nx receiving L-NAME reduced U_NOx. The addition of nipradilol increased U_NOx and decreased urinary protein excretion and glomerulosclerosis, suggesting that the NO released from the drug contributed to its renoprotective effect. Conclusion: These findings indicate that nipradilol exerts its renoprotective effect through NO generation, and not by lowering blood pressure. The β-adrenergic blocking action per se does not seem to be related to the renoprotective effect of these agents.

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Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

A Nitric Oxide-Generating Beta-Blocking Agent Prevents Renal Injury in the Rat Remnant Kidney Model

Takamitsu¹,

Nakanishi²,

Nishihara³

et al. 2003

Nephron Physiol

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“…Garg and Hassid [8]reported that cGMP-elevating vasodilators, which generate nitric oxide, inhibit mitogenesis and the proliferation of cultured smooth muscle cells. It was reported that cGMP inhibits MC proliferation [9, 10]and Nitta et al [11]reported that nipradiol inhibited DNA synthesis by increasing intracellular cGMP in cultured rat MC. However, the effects of nicorandil on MC proliferation have not been fully investigated.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Nicorandil on Rat Mesangial Cell Proliferation via the Protein Kinase G Pathway

Segawa

Minami²,

Shiga³

et al. 2001

Nephron

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We investigated the effects of nicorandil, which is a hybrid between a nitrate and an ATP-sensitive potassium channel (K_ATP) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 µM to 1 mM inhibited [³H]thymidine incorporation into rat mesangial cells in a concentration-dependent manner. Nicorandil (1 µM to 1 mM) also inhibited the number of cells. Nicorandil increased cyclic guanosine 3′,5′-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell proliferation. We also examined the effects of K_ATP mediators. Cromakalim, a K_ATP activator, and glibenclamide, a K_ATP inhibitor, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell proliferation are mediated via the protein kinase G pathway.

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“…Nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino)proxy-3-nitroxy-2H-1-benzopyran) is a nonselective adrenoreceptor blocking agent with weak β-adrenoreceptor blocking activity. This β-blocker has been shown to exert a direct vasodilating activity on glomerular afferent arterioles, as well as to increase glomerular blood flow (19) and to increase DNA synthesis when administered in conjunction with L-NAME (20). Since nipradilol contains an NO2 group within its molecular structure, it may release NO and affect glomerular function and structure.…”

Section: Introductionmentioning

confidence: 99%

Nipradilol Prevents L-NAME-Exacerbated Nephrosclerosis with Decreasing of Caspase-3 Expression in SHR.

et al. 2002

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Nipradilol inhibits DNA synthesis by regulating nitric oxide synthesis in cultured rat mesangial cells

Cited by 7 publications

References 6 publications

A Nitric Oxide-Generating Beta-Blocking Agent Prevents Renal Injury in the Rat Remnant Kidney Model

A Nitric Oxide-Generating Beta-Blocking Agent Prevents Renal Injury in the Rat Remnant Kidney Model

Inhibitory Effects of Nicorandil on Rat Mesangial Cell Proliferation via the Protein Kinase G Pathway

Nipradilol Prevents L-NAME-Exacerbated Nephrosclerosis with Decreasing of Caspase-3 Expression in SHR.

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