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In this study, we investigated the blood pressure responses of the peripheral bed in vivo after chronic hydrogen sulfide ([H.sub.2]S) inhibition combined with acute nitric oxide (NO) deficiency. We also evaluated the role of endogenously produced [H.sub.2]S in the vasoactive responses of large- and medium-sized arteries in vitro. Changes in integrated blood pressure responses were measured after chronic inhibition of cystathionine-[gamma]-lyase, an enzyme involved in [H.sub.2]S synthesis, with DL-propargylglycine (PPG), and acute inhibition of NO-synthase with nonspecific L-[N.sup.G]-nitro arginine methyl ester (L-NAME), and vasoactive responses of the thoracic aorta (TA) and mesenteric artery (MA) were investigated after acute incubation with PPG. We confirmed that chronic [H.sub.2]S deficiency had no effect on blood pressure, heart trophycity, noradrenaline, and [H.sub.2]S donor vasoactive responses but induced renal hypertrophy and a decrease in acetylcholine-induced hypotensive and L-NAME-induced hypertensive responses. Acute [H.sub.2]S deficiency led to an increase in basal tone (MA) or active tone (TA), whereas endothelium-dependent vasorelaxation remained unaffected. Long-term administration of PPG revealed a role of endogenous [H.sub.2]S in the bioavailability of endothelial NO in peripheral arteries. When both [H.sub.2]S and NO were lacking, the activation of [H.sub.2]S-independent compensatory mechanisms plays an important role in maintaining the vasodilator responses of the cardiovascular system. Key words: acute NO deficiency, chronic [H.sub.2]S deficiency, integrated responses, vasoactive responses. Cette etude portait sur les reactions pressives du lit sanguin peripherique in vivo apres une inhibition a long terme du sulfure d'hydrogene ([H.sub.2]S) associee avec une carence aigue en oxyde nitrique (NO). Nous avons aussi evalue le role du [H.sub.2]S endogene dans les reactions vasoactives des arteres de grandes et de moyennes tailles in vitro. Nous avons mesure les variations des reactions pressives integrees apres une inhibition a long terme de la cystathionine-y-lyase, une enzyme jouant un role dans la synthese du [H.sub.2]S, a l'aide de DL-propargylglycine (PPG), et evalue l'inhibition aigue de la NO synthase de maniere non specifique a l'aide de L-NAME (pour << L-[N.sup.G]-nitro arginine methyl ester >>); nous avons aussi etudie les reactions vasoactives de l'aorte thoracique (AT) et de l'artere mesenterique (AM) apres une incubation aigue avec de la PPG. Nous avons confirme que la carence en [H.sub.2]S a long terme n'avait aucun effet sur la tension arterielle, la trophicite du coeur, les reactions vasoactives a la noradrenaline et au donneur de [H.sub.2]S, mais qu'elle entrainait une hypertrophie renale ainsi qu'une diminution des reactions hypotensives engendrees par l'acetylcholine et des reactions hypertensives engendrees par le L-NAME. La carence aigue en [H.sub.2]S a mene a une augmentation du tonus basal (AM) ou du tonus actif (AT), mais sans consequences sur la vasorelaxation dependante de l'endothelium. L'administration a long terme de PPG a revele le role du [H.sub.2]S endogene quant a la biodisponibilite du NO endothelial dans les arteres peripheriques. En etat de carence en [H.sub.2]S et en NO, l'activation des modes d'action compensatoires independants du [H.sub.2]S jouait un role important dans le maintien des reactions vasodilatatrices du systeme cardiovasculaire. [Traduit par la Redaction] Mots-cles : carence aigue en NO, carence en [H.sub.2]S a long terme, reactions integrees, reactions vasoactives., Introduction The circulation system ensures adequate perfusion to meet the metabolic requirements of tissues. Among others, the endogenous gasotransmitters nitric oxide (NO) and hydrogen sulfide ([H.sub.2]S) are involved in the [...]

Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide (H2S). We investigated whether a slow-releasing H2S donor, GYY-4137, could exert beneficial activity in these conditions. We examined the effect of eight weeks of fructose intake on the blood pressure, biometric parameters, vasoactive responses, and NO and H2S pathways in fructose-fed spontaneously hypertensive rats with or without three weeks of GYY-4137 i.p. application. GYY-4137 reduced triacylglycerol levels and blood pressure, but not adiposity, and all were increased by fructose intake. Fructose intake generally enhanced endothelium-dependent vasorelaxation, decreased adrenergic contraction, and increased protein expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and concentration of conjugated dienes in the left ventricle (LV). Although GYY-4137 administration did not affect vasorelaxant responses, it restored disturbed contractility, LV oxidative damage and decreased protein expression of TNFα in fructose-fed rats. While the participation of endogenous H2S in vasoactive responses was not affected by fructose treatment, the expression of H2S-producing enzyme cystathionine β-synthase in the LV was increased, and the stimulation of the NO signaling pathway improved endothelial function in the mesenteric artery. On the other hand, chronic treatment with GYY-4137 increased the expression of H2S-producing enzyme cystathionine γ-lyase in the LV and stimulated the beneficial pro-relaxant and anti-contractile activity of endogenous H2S in thoracic aorta. Our results suggest that sulfide and nitroso signaling pathways could trigger compensatory vasoactive responses in hypertensive rats with metabolic disorder. A slow H2S-releasing donor could partially amend metabolic-related changes and trigger beneficial activity of endogenous H2S. [ABSTRACT FROM AUTHOR]

The importance of disclosing the various effects of the inhibition of angiotensin-converting enzyme-2 (ACE2) in regulation of vascular tone has been shown during the COVID-19 pandemic. Various substances with antioxidant properties were proposed to have a beneficial effect in mitigating the progress of COVID-19. Therefore, we have investigated the effect of 14-day ACE2 inhibitor MLN-4760 treatment (s.c.) and 10-day oral coadministration of taxifolin (TAX) on the regulation of vascular tone of isolated femoral arteries. Our results showed that the ACE2 inhibitor MLN-4760 enhanced the maximal noradrenalin-induced contraction as well as the sensitivity to noradrenalin (NA). The acetylcholine-induced endothelium-dependent relaxation was not changed after MLN-4760 administration, but the acetylcholine-induced endothelium-dependent contraction was augmented. TAX administration reduced the maximal NA-induced contraction, but did not change the sensitivity to NA. The endothelium-dependent relaxation was improved after TAX application as shown by the calculation of area under the curve. TAX did not influence the acetylcholine-induced endothelium-dependent contraction. In conclusion, administration of MLN-4760 leads to increased NA-induced contraction of femoral arteries, which can be partially mediated through increased endotheliumdependent contraction. TAX mitigated the enhanced NA-induced contraction caused by MLN-4760 administration, but did not affect endothelium-dependent contraction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Isolated tissue chamber bath system and wire myograph were developed for "in vitro" investigation of vasoactive responses on isolated arteries from a variety of animal species and vascular beds. The chapter characterizes the main principles of mechanical measurement of the changes in isometric tension of vascular smooth muscles in isolated rat thoracic aorta and superior mesenteric artery and describes several protocols on how to investigate vasoactive properties of hydrogen sulfide (H 2 S) from the point of view of its mutual interaction with NO. Several methodological advances, results, and their interpretations in the context of the general knowledge are described. In the protocols the approach on how to study the vasoactive modulatory as well as direct action of H 2 S and mutual interaction of H 2 S with nitroso compounds, lipids, and endogenously produced NO is described.