Modulation of endothelin-1-induced contractions by magnesium/calcium in porcine ciliary arteries

Dettmann, Eike S.; Lüscher, Thomas F.; Haefliger, Ivan O.

doi:10.1007/s004170050041

Cited by 34 publications

(33 citation statements)

References 25 publications

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“…U46619 causes an increased calcium entry in vascular smooth muscle (12). As both nifedipine (8) and extracellular calcium depletion do not prevent the hypoxic augmentation, an increased calcium influx cannot not explain the current phenomenon.…”

Section: Discussionmentioning

confidence: 78%

Endothelium-derived NO, but not cyclic GMP, is required for hypoxic augmentation in isolated porcine coronary arteries

Chan¹,

Mak

Gao

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Chan CK, Mak J, Gao Y, Man RY, Vanhoutte PM. Endotheliumderived NO, but not cyclic GMP, is required for hypoxic augmentation in isolated porcine coronary arteries. Am J Physiol Heart Circ Physiol 301: H2313-H2321, 2011. First published October 7, 2011 doi:10.1152/ajpheart.00258.2011.-The present study investigated the mechanism underlying the transient potentiation of vasoconstriction by hypoxia in isolated porcine coronary arteries. Isometric tension was measured in rings with or without endothelium. Hypoxia (PO2 Ͻ30 mmHg) caused a transient further increase in tension (hypoxic augmentation) in contracted (with U46619) preparations. The hypoxic response was endothelium dependent and abolished by inhibitors of nitric oxide synthase [N -nitro-L-arginine methyl ester (L-NAME)] or soluble guanylyl cyclase (ODQ and NS2028). The addition of DETA NONOate (nitric oxide donor) in the presence of L-NAME restored the hypoxic augmentation, suggesting the involvement of the nitric oxide pathway. However, the same was not observed after incubation with 8-bromo-cyclic GMP, atrial natriuretic peptide, or isoproterenol. Assay of the cyclic GMP content showed no change upon exposure to hypoxia in preparations with and without endothelium. Incubation with protein kinase G and protein kinase A inhibitors did not inhibit the hypoxic augmentation. Thus the hypoxic augmentation is dependent on nitric oxide and soluble guanylyl cyclase but independent of cyclic GMP. The hypoxic augmentation persisted in calcium-free buffer and in the presence of nifedipine, ruling out a role for extracellular calcium influx. Hypoxia did not alter the intracellular calcium concentration, as measured by confocal fluorescence microscopy. This observation and the findings that hypoxic augmentation is enhanced by thapsigargin (sarco/endoplasmic reticulum calcium ATPase inhibitor) and inhibited by HA1077 or Y27632 (Rho kinase inhibitors) demonstrate the involvement of calcium sensitization in the phenomenon. soluble guanylyl cyclase; calcium sensitization; nitric oxide ENDOTHELIUM-DEPENDENT AUGMENTATION of contraction by hypoxia has been observed in canine femoral and coronary arteries (10,22,41), in the rat mesenteric artery (57), and in the human coronary artery (56). In the dog, augmented hypoxic coronary vasoconstrictions, which significantly reduce the blood supply to the cardiac muscle, occur in vivo only after previous ischemia-reperfusion injury (41). Considering that the hypoxic augmentation can be repeated consistently even after several episodes of exposure to hypoxia (10), this phenomenon could be important in patients (particularly if they have a previous history of coronary disease) exposed to repeated episodes of reduced oxygen content in the blood, as in the case for example in sleep apnea.The exact mechanism underlying hypoxic endothelium-dependent augmentation of vasoconstriction is not fully understood. Bioassay studies (45) on canine coronary arteries demonstrated that a diffusible substance released by the endothelium contributes to th...

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Section: Discussionmentioning

confidence: 78%

Endothelium-derived NO, but not cyclic GMP, is required for hypoxic augmentation in isolated porcine coronary arteries

Chan¹,

Mak

Gao

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Mg 2+ is known widely to modulate vascular smooth muscle contraction and tone, thus influencing the blood pressure [3,31,49]. Increased extracellular [Mg 2+ ] ([Mg 2+ ] o ) attenuates agonist-induced vasoconstriction, whereas decreasing the concentration potentiates the effects of various vasoconstrictors [4,10,17,23,43].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Mg2+ blocks endothelin-1-induced contraction through the inhibition of non-selective cation channels in coronary smooth muscle

Park

Earm

2004

Pflugers Arch - Eur J Physiol

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This study investigated the effects of changing the extracellular [Mg(2+)] ([Mg(2+)](o)) on endothelin-1 (ET-1)-induced contraction of rabbit coronary artery smooth muscle and the involvement of non-selective cation (NSC) channels in this response. Increased [Mg(2+)](o) shifted the concentration/contraction relationship curve of ET-1 to the right. In whole-cell patch clamp recordings, ET-1 (10(-7) M) induced a long-lasting inwards current (94.7+/-7.2 pA) that was inhibited by 8 mM [Mg(2+)](o) (45.3+/-4.4%) and NSC channel blockers (10(-3) M streptomycin and 10(-3) M La(3+)), but not by the voltage-dependent Ca(2+) channel blocker nicardipine. The current/voltage (I/V) curve was linear. Furthermore, in pressurized arteries, the ET-1-induced contraction was also inhibited by La(3+) and streptomycin, but not by nicardipine. U-73122, a selective phospholipase C (PLC) inhibitor and staurosporine and GF 109203X, which block protein kinase C (PKC), reduced ET-1-activated NSC currents by 54.2+/-5.1%, 60.3+/-5.5% and 48.5+/-2.9%, respectively. The inwards current was increased by 1-oleoyl-2-acetyl-sn-glycerol (OAG) and phorbol 12,13-dibutyrate (PDBu), which activate PKC selectively. Like transient receptor potential channel (TRPC3) currents, ET-1-activated NSC currents had a linear I/V relationship, were blocked by flufenamate and activated by a diacylglycerol analogue. These results suggest that [Mg(2+)](o) blocks ET-1-induced contraction of coronary arteries by inhibiting NSC channels. Activation of PLC and PKC might be involved in activation of NSC channels.

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“…Magnesium is a physiological calcium channel blocker that partially inhibits the effect of endothelin-1 [14] and improves blood flow [13]. A dosage of 10-20 mmol daily is recommended for adults to improve the regulation of blood flow [13,99].…”

Section: Magnesiummentioning

confidence: 99%

“…In Europe, we are slowly going to where the Eastern culture has been for hundreds of years back to the idea that food is medicine and that we cannot disassociate our health with what we eat. As ophthalmologists, we are doing no harm to the patient by providing them with additional information on nutrition and lifestyle for the following reasons: it is cheap, well accepted by the patient as it has a natural source and supports the FS patient with their subjective symptoms with some first studies showing objective improvements in measures such as increased retinal venous pressure [5,6], decreased systemic oxidative stress or improvements in peripheral blood flow [12][13][14]. It is important to note, however, that nutritional recommendations for people with FS are quite different than those with a metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

Nutritional recommendations for individuals with Flammer syndrome

et al. 2017

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The Flammer syndrome (FS) describes the phenotype of people with a predisposition for an altered reaction of the blood vessels to stimuli like coldness or emotional stress.The question whether such people should be treated is often discussed. On the one hand, most of these subjects are healthy; on the other hand, FS seems to predispose to certain eye diseases such as normal tension glaucoma or retinitis pigmentosa or systemic diseases such as multiple sclerosis or tinnitus. A compromise between doing nothing and a drug treatment is the adaption of nutrition. But what do we mean by healthy food consumption for subjects with FS? The adaption of nutrition depends on the health condition. Whereas patients with e.g. a metabolic syndrome should reduce their calorie intake, this can be counterproductive for subjects with FS, as most subjects with FS have already a low body mass index (BMI) and the lower the BMI the stronger the FS symptoms. Accordingly, while fasting is healthy e.g. for subjects with metabolic syndrome, fasting can even dangerously aggravate the vascular dysregulation, as it has been nicely demonstrated by the loss of retinal vascular regulation during fasting. To give another example, while reducing salt intake is recommended for subjects with systemic hypertensions, such a salt restriction can aggravate systemic hypotension and thereby indirectly also the vascular regulation in subjects with FS. This clearly demonstrates that such a preventive adaption of nutrition needs to be personalized.

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Modulation of endothelin-1-induced contractions by magnesium/calcium in porcine ciliary arteries

Abstract: In a mechanism which appears to be compatible with a calcium-antagonist effect, magnesium strongly modulates changes in contractile tone evoked by endothelin-1, but has no effect on bradykinin-induced relaxations.

Cited by 34 publications

References 25 publications

Endothelium-derived NO, but not cyclic GMP, is required for hypoxic augmentation in isolated porcine coronary arteries

Endothelium-derived NO, but not cyclic GMP, is required for hypoxic augmentation in isolated porcine coronary arteries

Extracellular Mg2+ blocks endothelin-1-induced contraction through the inhibition of non-selective cation channels in coronary smooth muscle

Nutritional recommendations for individuals with Flammer syndrome

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