Sodium nitroprusside and other smooth muscle-relaxants increase cyclic GMP levels in rat ductus deferens

Schultz, Karin; Schultz, Günter

doi:10.1038/265750a0

Cited by 423 publications

(153 citation statements)

References 16 publications

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“…Similar results have been obtained after combined administration of glyceryl trinitrate, which stimulates guanylate cyclase in blood vessels (Schultz et al, 1977) and the selective cyclic GMP-phosphodiesterase inhibitor, M&B 22948 (Kukovetz et al, 1979;Martin et al, 1986). Furthermore, the antagonistic effect of carbenoxolone on the action of oxyhaemoglobin on RPN-and SIN-1-induced inhibition of platelet aggregation resembles that of IBMX and is compatible with phosphodiesterase inhibition (Salvemini et al, 1990).…”

Section: Resultssupporting

confidence: 69%

Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection

Dembińska-Kieć

Pallapies

Simmet

et al. 1991

British J Pharmacology

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1 The interactions between carbenoxolone and nitric oxide (NO) were examined by investigating their effects on human platelet aggregation, on rat aortic strips precontracted by phenylephrine and on protection of rat gastric mucosa against ethanol-induced injury.2 Carbenoxolone (100-300,UM) caused a significant and concentration-dependent potentiation of rat peritoneal neutrophil (RPN)-, 3-morpholino-sydnonimine (SIN-1)-or iloprost-induced inhibition of platelet aggregation. Higher concentrations (5001uM) of carbenoxolone alone markedly inhibited platelet aggregation. Pretreatment with carbenoxolone (100-300pM) antagonized the reversal of the RPN-or SIN-1-induced antiaggregatory effect by oxyhaemoglobin (10Mm).3 Rat aortic strips with intact endothelium precontracted by phenylephrine (0.1-0.31uM) were relaxed by carbenoxolone (100-300,uM) in a concentration-dependent manner. Relaxations were abolished by mechanical removal of the endothelium or by incubation with methylene blue (10pM) or NG-nitro-L-arginine (L-NNA, 100pgM). Sodium nitroprusside (10 nM)-induced relaxations of endothelium-denuded rat aortic strips were potentiated by carbenoxolone (100 UM). 4 The carbenoxolone (200mg kg-1, p.o.)-induced gastroprotection against ethanol was antagonized by L-NNA (5-4Omgkg-1) in a dose-dependent manner. Pretreatment of rats with indomethacin (lOmgkg 1, s.c.) increased the effect of L-NNA. 5 The results suggest that the activity of carbenoxolone in the experimental systems tested is due to phosphodiesterase inhibition, although radical scavenging properties of the drug could contribute to some of the effects observed. In the rat gastric mucosa both increased prostaglandin levels and effects on the NO system could contribute to the protective action of carbenoxolone.

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Section: Resultssupporting

confidence: 69%

Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection

Dembińska-Kieć

Pallapies

Simmet

et al. 1991

British J Pharmacology

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“…29 Finally, endothelium-independent vasodilation was assessed with sodium nitroprusside (1, 2, and 4 g/100 mL per minute for 5 minutes, each dose). 30 L-NMMA, ouabain, and vitamin C were started 10 minutes before bradykinin and continued throughout. Thirty minutes' washout was allowed between each infusion, whereas a 60-minute period was allowed after L-NMMA.…”

Section: Experimental Modelmentioning

confidence: 99%

Calcium Antagonist Treatment by Lercanidipine Prevents Hyperpolarization in Essential Hypertension

et al. 2003

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Abstract-Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxidative stress-induced nitric oxide (NO) breakdown and compensatory production of a hyperpolarizing factor. To test whether calcium antagonist treatment can restore NO availability and prevent hyperpolarization through antioxidant properties, in 15 healthy subjects and 15 patients with essential hypertension, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial bradykinin (5, 15, 50 ng/100 mL per minute), an endothelium-dependent vasodilator, in basal conditions, during infusion of N G -monomethyl-L-arginine (L-NMMA, 100 g/100 mL per minute), an NO-synthase inhibitor, and ouabain (0.72 g/100 mL per minute), an Na ϩ -K ϩ ATPase inhibitor to prevent hyperpolarization. These infusions were repeated in the presence of the antioxidant vitamin C (8 mg/100 mL/min). The response to sodium nitroprusside was also evaluated. In controls, vasodilation to bradykinin was inhibited by L-NMMA and remained unchanged by ouabain or vitamin C. In hypertensive patients, vasodilation to bradykinin was blunted and resistant to L-NMMA but sensitive to ouabain. Vitamin C increased the response to bradykinin and restored the inhibiting effect of L-NMMA while preventing the effect of ouabain. In hypertensive patients, infusions were repeated after 3-month treatment with lercanidipine (10 to 20 mg daily). Lercanidipine decreased plasma lipoperoxides, isoprostanes, and malondialdehyde and increased plasma antioxidant capacity. Moreover, lercanidipine increased the vasodilation to bradykinin and restored the inhibiting effect of L-NMMA on bradykinin-induced vasodilation while preventing the effect of ouabain. Finally, vitamin C no longer exerted its facilitating activity. These results indicate that in essential hypertension, lercanidipine increases endothelium-dependent vasodilation by restoring NO availability and preventing hyperpolarization, an effect probably determined by antioxidant activity. Key Words: hypertension, essential Ⅲ endothelium Ⅲ nitric oxide Ⅲ endothelium-derived factors Ⅲ free radicals Ⅲ antioxidants Ⅲ calcium antagonists E ndothelium plays a primary role in the modulation of vascular tone 1 by producing and releasing relaxing substances including nitric oxide (NO) 2 and a not-yet identified hyperpolarizing factor (EDHF). 3 In the presence of several cardiovascular risk factors, endothelial cells can also produce contracting factors (EDCFs), which are mainly cyclooxygenase-dependent prostanoids (thromboxane A2 and prostaglandin H2) 4,5 or superoxide anions. 6 Essential hypertension is characterized by impaired endothelium-dependent vasodilation to specific agonists 7-9 as the result of a reduction in NO oxide availability 10,11 caused by production of oxidative stress. 12 In the presence of impaired NO availability, endothelium-dependent relaxation seems to be sustained by hyperpolarization, which probably acts as a compensatory mechanism. 13 Since endothelial dysfunct...

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“…Pericytes and vascular smooth muscle cells are related by a similar topography in the wall of the vessel (1), and a biochemical relationship between the two cell types is suggested by the immunocytochemical localization in both cells of cyclic GMP-dependent protein kinase (17), an enzyme believed to function in the regulation of smooth muscle cell contractility (13,28,30), and of the intermediate filament proteins desmin and vimentin (9). To explore this relationship further and to provide evidence for the presence in pericytes of additional contraction-associated proteins, we extended the inquiry to tropomyosin, a protein considered essential for the regulation of cellular contractility.…”

mentioning

confidence: 99%

Contractile proteins in pericytes. I. Immunoperoxidase localization of tropomyosin.

Joyce¹,

Haire²,

Palade³

1985

The Journal of Cell Biology

147

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In these studies we have compared the relative amounts and isoforms of tropomyosin in capillary and postcapillary venule pericytes, endothelial cells, and vascular smooth muscle cells in four rat microvascular beds: heart, diaphragm, pancreas, and the intestinal mucosa. The results, obtained by in situ immunoperoxidase localization, indicate that (a) tropomyosin is present in capillary and postcapillary venule pericytes in relatively high concentration; (b) the tropomyosin content of pericytes appears to be somewhat lower than in vascular smooth muscle cells but higher than in endothelia and other vessel-associated cells; and (c) pericytes, unlike endothelia and other nonmuscle cells, contain detectable levels of tropomyosin immunologically related to the smooth muscle isoform. These results and our previous findings concerning the presence of a cyclic GMP-dependent protein kinase (Joyce, N., P. DeCamilli, and J. Boyles, 1984, Microvasc. Res. 28:206-219) in pericytes demonstrate that these cells contain significant amounts of at least two proteins important for contraction regulation. Taken together, the evidence suggests that pericytes are contractile elements related to vascular smooth muscle cells, possibly involved, as are the latter, in the regulation of blood flow through the microvasculature.Pericytes are polymorphic cells closely associated with the walls of capillaries and postcapillary venules. They have a cell body which is often highly elongated, and multiple branching foot processes which partially encircle the vessel wall. Pericytes can be distinguished from other perivascular cells, such as adventitial fibroblasts, by their location within the basement membrane of the vessels, and by the close apposition of the tips of their processes to the underlying endothelium. Electron microscopic studies have identified pericytes in a number of tissues and organs (I0, 12, 20, 36). They may, in fact, be common to all microvascular beds, although their relative frequency and distribution appear to vary from one microvascular bed to another (32,33).The function of pericytes is still unclear; however, morphologic evidence suggests that they may be contractile cells related to vascular smooth muscle. Numerous micro filaments form a continuous plate in the adluminal cytoplasm of their cell body and extend from it into the foot processes, where, in the more distal segments, they fill the cytoplasm to the relative exclusion of other subeellular components. In addition, the foot processes have densities that appear similar to the attachment plaques and dense bodies of smooth muscle cells (29,32,34). The presence of such structures within circumferentially oriented pericyte processes suggests a poten-

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Sodium nitroprusside and other smooth muscle-relaxants increase cyclic GMP levels in rat ductus deferens

Cited by 423 publications

References 16 publications

Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection

Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection

Calcium Antagonist Treatment by Lercanidipine Prevents Hyperpolarization in Essential Hypertension

Contractile proteins in pericytes. I. Immunoperoxidase localization of tropomyosin.

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