Fructose Intake Impairs the Synergistic Vasomotor Manifestation of Nitric Oxide and Hydrogen Sulfide in Rat Aorta

Berenyiová, Andrea; Golas, Samuel; Drobna, Magdalena; Cebová, Martina; Čačányiová, Soňa

doi:10.3390/ijms22094749

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…Nevertheless, we confirmed that, unlike in control rats, H 2 S significantly participated in maintaining endothelial function in the MLN-4760 group (unlike in the control group). Similar compensatory crosstalk between NO and H 2 S signaling has already been declared in fructose-fed normotensive rats [ 62 ] as well as in SHRs, where the increased participation of H 2 S in vasorelaxation after acute NO inhibition could be considered a salvage mechanism in cases of endogenous NO deficiency [ 10 ]. Similarly, we confirmed a stronger anticontractile action of H 2 S produced by perivascular adipose tissue surrounding the thoracic aorta in hypertriglyceridemic rats [ 63 ], suggesting that H 2 S signaling can be stimulated as a balancing pathway in different pathological conditions.…”

Section: Discussionsupporting

confidence: 56%

Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

et al. 2021

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects host cells through angiotensin-converting enzyme 2 (ACE2). Concurrently, the product of ACE2 action, angiotensin 1–7 (Ang 1–7), binds to Mas receptors within the cardiovascular system and provides protective effects. Therefore, it is crucial to reveal the role of ACE2 inhibition, especially within pre-existing cardiovascular pathologies. In our study, we imitated the action of SARS-CoV-2 in organisms using the low dose of the ACE2 inhibitor MLN-4760 with the aim of investigating to what degree ACE2 inhibition is detrimental to the cardiovascular system of spontaneously hypertensive rats (SHRs), which represent a model of human essential hypertension. Our study revealed the complex action of MLN-4760 in SHRs. On the one hand, we found that MLN-4760 had 1) (pro)obesogenic effects that negatively correlated with alternative renin-angiotensin system activity and Ang 1–7 in plasma, 2) negative effects on ACE1 inhibitor (captopril) action, 3) detrimental effects on the small arteries function and 4) anti-angiogenic effect in the model of chick chorioallantoic membrane. On the other hand, MLN-4760 induced compensatory mechanisms involving strengthened Mas receptor-, nitric oxide- and hydrogen sulfide-mediated signal transduction in the aorta, which was associated with unchanged blood pressure, suggesting beneficial action of MLN-4760 when administered at a low dose.

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Section: Discussionsupporting

confidence: 56%

Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

et al. 2021

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“…Incubation with the H 2 S scavenger reduced endothelium-dependent relaxation in all experimental groups, except for the control SHR, and ZOFE treatment had no effect on these vasoactive responses, suggesting that H 2 S participated in maintaining endothelial function in MLN-treated rats, which could be considered a compensatory mechanism. This observation corresponds with other findings that declare that H 2 S signaling can be stimulated in different pathological conditions, e.g., in fructose-fed normotensive rats [ 58 ] as well as in SHRs, where the increased participation of H 2 S in vasorelaxation could counterbalance endogenous NO deficiency [ 53 ]. The decreased expression of H 2 S-producing enzymes in the MLN-treated rats could be explained by negative feedback regulation to maintain a constant H 2 S level.…”

Section: Discussionsupporting

confidence: 91%

The effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats treated with the ACE2 inhibitor MLN-4760

Cacanyiova,

Cebova,

Simko

et al. 2023

Biol Res

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Background Angiotensin converting enzyme 2 (ACE2) plays a crucial role in the infection cycle of SARS-CoV-2 responsible for formation of COVID-19 pandemic. In the cardiovascular system, the virus enters the cells by binding to the transmembrane form of ACE2 causing detrimental effects especially in individuals with developed hypertension or heart disease. Zofenopril, a H2S-releasing angiotensin-converting enzyme inhibitor (ACEI), has been shown to be effective in the treatment of patients with essential hypertension; however, in conditions of ACE2 inhibition its potential beneficial effect has not been investigated yet. Therefore, the aim of the study was to determine the effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats, an animal model of human essential hypertension and heart failure, under conditions of ACE2 inhibition induced by the administration of the specific inhibitor MLN-4760 (MLN). Results Zofenopril reduced MLN-increased visceral fat to body weight ratio although no changes in systolic blood pressure were recorded. Zofenopril administration resulted in a favorable increase in left ventricle ejection fraction and improvement of diastolic function regardless of ACE2 inhibition, which was associated with increased H2S levels in plasma and heart tissue. Similarly, the acute hypotensive responses induced by acetylcholine, L-NAME (NOsynthase inhibitor) and captopril (ACEI) were comparable after zofenopril administration independently from ACE2 inhibition. Although simultaneous treatment with zofenopril and MLN led to increased thoracic aorta vasorelaxation, zofenopril increased the NO component equally regardless of MLN treatment, which was associated with increased NO-synthase activity in aorta and left ventricle. Moreover, unlike in control rats, the endogenous H2S participated in maintaining of aortic endothelial function in MLN-treated rats and the treatment with zofenopril had no impact on this effect. Conclusions Zofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H2S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2 inhibition itself can lead to the activation of cardiovascular compensatory mechanisms associated with Mas receptor, nitrous and sulfide signaling.

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“…Arterial endothelial dysfunction was described in studies using different fructose-fed protocols, and it was related to increased oxidative stress, reduced production or availability of nitric oxide, and increased levels of uric acid and endothelin-1 [ 41 , 42 , 43 ]. The presented results as well as the observations of other authors demonstrate that the substances released from PVAT could participate in these pathological processes [ 17 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Perivascular Adipose Tissue in Early Changes in Arterial Function during High-Fat Diet and Its Combination with High-Fructose Intake in Rats

et al. 2021

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The aim of the current study was to evaluate the influence of a high-fat diet and its combination with high-fructose intake on young normotensive rats, with focus on the modulatory effect of perivascular adipose tissue (PVAT) on the reactivity of isolated arteries. Six-week-old Wistar–Kyoto rats were treated for 8 weeks with a control diet (10% fat), a high-fat diet (HFD; 45% fat), or a combination of the HFD with a 10% solution of fructose. Contractile and relaxant responses of isolated rat arteries, with preserved and removed PVAT for selected vasoactive stimuli, were recorded isometrically by a force displacement transducer. The results demonstrated that, in young rats, eight weeks of the HFD might lead to body fat accumulation and early excitation of the cardiovascular sympathetic nervous system, as shown by increased heart rate and enhanced arterial contractile responses induced by endogenous noradrenaline released from perivascular sympathetic nerves. The addition of high-fructose intake deteriorated this state by impairment of arterial relaxation and resulted in mild elevation of systolic blood pressure; however, the increase in arterial neurogenic contractions was not detected. The diet-induced alterations in isolated arteries were observed only in the presence of PVAT, indicating that this structure is important in initiation of early vascular changes during the development of metabolic syndrome.

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Fructose Intake Impairs the Synergistic Vasomotor Manifestation of Nitric Oxide and Hydrogen Sulfide in Rat Aorta

Cited by 8 publications

References 37 publications

Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

The effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats treated with the ACE2 inhibitor MLN-4760

The Role of Perivascular Adipose Tissue in Early Changes in Arterial Function during High-Fat Diet and Its Combination with High-Fructose Intake in Rats

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