Different patterns of H2S/NO activity and cross-talk in the control of the coronary vascular bed under normotensive or hypertensive conditions

Testai, Lara; D’Antongiovanni, Vanessa; Piano, Ilaria; Martelli, Alma; Citi, Valentina; Duranti, Emiliano; Virdis, Agostino; Blandizzi, Corrado; Gargini, Claudia; Breschi, Maria Cristina; Calderone, Vincenzo

doi:10.1016/j.niox.2015.03.003

Cited by 30 publications

(20 citation statements)

References 46 publications

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“…However, irrespective of the potential role of endogenous H 2 S, in the above experimental studies, the administration of exogenous H 2 S donors always caused a reduction in vascular resistance and a significant increase in CF. This feature had been observed previously for synthetic aryl-isothiocyanate H 2 S donors Testai et al, 2015). These effects suggest a possible utility for H 2 S donors in coronary artery diseases.…”

Section: Discussionsupporting

confidence: 83%

Erucin exhibits vasorelaxing effects and antihypertensive activity by H₂S‐releasing properties

Martelli

Piragine

Citi

et al. 2019

British J Pharmacology

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Background and Purpose Hydrogen sulfide (H2S)‐releasing agents are viewed as potential antihypertensive drugs. Recently, natural isothiocyanates emerged as original H2S‐donor agents. Among them, erucin, present in some edible cruciferous plants, shows suitable H2S‐releasing properties and features of “druggability.” The aim of this work was to investigate the erucin‐mediated release of H2S inside vascular cells, its vasorelaxing effects, and activity on BP of normo and hypertensive animals. Experimental Approach Intracellular H2S‐release and the hyperpolarizing effect of erucin were tested using fluorescent dye, in human aortic smooth muscle cells (HASMCs). Its direct vasorelaxing effect and ability to inhibit noradrenaline‐induced vasoconstriction were evaluated on endothelium‐intact or ‐denuded rat aortic rings. Its vasodilator properties were tested in coronary arteries using Langendorff‐perfused rat hearts. Finally, erucin's antihypertensive activity was evaluated in vivo in normotensive and spontaneously hypertensive rats (SHRs) by recording systolic BP using the tail‐cuff method. Key Results Erucin induced the release of H2S inside HASMCs. Moreover, erucin hyperpolarized the membrane of HASMCs membrane in a concentration‐dependent manner. It induced vasodilatation of rat aortic rings, in endothelium‐denuded vessels. This effect was further improved by the presence of endothelial NO. When pre‐incubated with rat aortic rings, erucin induced concentration‐dependent inhibition of noradrenaline‐induced vasoconstriction. Erucin did not affect basal coronary flow but restored the flow to normal in pre‐contracted coronary vessels. Finally, in vivo, erucin decreased systolic BP in SHRs by about 25%, and restored the BP to values observed in normotensive rats. Conclusions and Implications Erucin is an H2S donor endowed with vasorelaxing and antihypertensive effects. Linked Articles This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc

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Section: Discussionsupporting

confidence: 83%

Erucin exhibits vasorelaxing effects and antihypertensive activity by H₂S‐releasing properties

Martelli

Piragine

Citi

et al. 2019

British J Pharmacology

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“…However, other studies showed that in normotensive rats, the vascular actions of H 2 S required nitric oxide and vice versa. In contrast, in spontaneously hypertensive rats, the H 2 S-induced actions scarcely depend on nitric oxide release; also, the nitric oxide effects are largely H 2 S-independent and represent the first step for understanding pathophysiological mechanisms of nitric oxide/H 2 S interplays under both normotensive and hypertensive conditions [31]. Terminalia bellirica is also shown to have antihypertensive [17] and antioxidant [32] activity.…”

Section: Discussionmentioning

confidence: 99%

Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol. ex. Maton in Rats

Sholikhah

Mustofa

Nugrahaningsih

et al. 2020

BioMed Research International

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The polyherbal formulation containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol ex. Maton has been used for hypertension treatment empirically. Our previous study showed its blood pressure-lowering effect on a rat model of hypertension. However, toxicity data were not available for this polyherbal formulation. This study is aimed at evaluating the acute and subchronic oral toxicity of the polyherbal formulation in rats. The acute toxicity study was conducted on 6 female Wistar rats using the fixed-dose method for the treatment group and 5 female Wistar rats for the control. The single dose of 2,000 mg/kg of the polyherbal formulation was given orally. There were no significant toxic effects and no death observed until the end of the study, and it was showed that the lethal dose 50% (LD50) of the polyherbal formulation was estimated to be more than 2,000 mg/kg. The macroscopic and microscopic examination of vital organs showed no symptoms of toxicity. At the subchronic toxicity study, the polyherbal formulation with 3 dose variations of 252 mg/kg, 1,008 mg/kg, and 4,032 mg/kg was administered for 91 days orally. The lowest dose of 252 mg/kg is equivalent to the daily recommended dose for a human. There were no significant toxic effects observed at all doses on physical sign and symptoms, weight gain, food intake, hematological parameters, biochemical parameters, and macroscopic and microscopic examination of organs. These findings showed that the short- and long-term oral administration of the polyherbal formulation is safe to use within its dose recommendation.

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“…Furthermore, ROS inhibit vascular smooth muscle cell hyperpolarization and reduces H 2 S-mediated relaxation, supporting the arterial constriction. The effect of ROS on vascular function may be accentuated after inhibition of NO production that may result in elevated bioavailability of superoxide (Testai et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Lack of Reactive Oxygen Species Deteriorates Blood Pressure Regulation in Acute Stress

Bernátová

Bališ²,

Goga³

et al. 2016

Physiol Res

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This study investigated the contribution of reactive oxygen species (ROS) to blood pressure regulation in conscious adult male Wistar rats exposed to acute stress. Role of ROS was investigated in rats with temporally impaired principal blood pressure regulation systems using ganglionic blocker pentolinium (P, 5 mg/kg), angiotensin converting enzyme inhibitor captopril (C, 10 mg/kg), nitric oxide synthase inhibitor L-NAME (L, 30 mg/kg) and superoxide dismutase mimeticum tempol (T, 25 mg/kg). Mean arterial pressure (MAP) was measured by the carotid artery catheter and inhibitors were administered intravenously. MAP was disturbed by a 3-s air jet, which increased MAP by 35.2±3.0 % vs. basal MAP after the first exposure. Air jet increased MAP in captopril-and tempol-treated rats similarly as observed in saline-treated rats. In pentoliniumtreated rats stress significantly decreased MAP vs. pre-stress value. In L-NAME-treated rats stress failed to affect MAP significantly. Treatment of rats with P+L+C resulted in stressinduced MAP decrease by 17.3±1.3 % vs. pre-stress value and settling time (20.1±4.2 s). In P+L+C+T-treated rats stress led to maximal MAP decrease by 26.4±2.2 % (p<0.005 vs. P+L+C) and prolongation of settling time to 32.6±3.3 s (p<0.05 vs. P+L+C).Area under the MAP curve was significantly smaller in P+L+Ctreated rats compared to P+L+C+T-treated ones (167±43 vs. 433±69 a.u., p<0.008). In conclusion, in rats with temporally impaired blood pressure regulation, the lack of ROS resulted in greater stress-induced MAP alterations and prolongation of time required to reach new post-stress steady state.

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Different patterns of H2S/NO activity and cross-talk in the control of the coronary vascular bed under normotensive or hypertensive conditions

Cited by 30 publications

References 46 publications

Erucin exhibits vasorelaxing effects and antihypertensive activity by H₂S‐releasing properties

Erucin exhibits vasorelaxing effects and antihypertensive activity by H₂S‐releasing properties

Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol. ex. Maton in Rats

Lack of Reactive Oxygen Species Deteriorates Blood Pressure Regulation in Acute Stress

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Different patterns of H2S/NO activity and cross-talk in the control of the coronary vascular bed under normotensive or hypertensive conditions

Cited by 30 publications

References 46 publications

Erucin exhibits vasorelaxing effects and antihypertensive activity by H2S‐releasing properties

Erucin exhibits vasorelaxing effects and antihypertensive activity by H2S‐releasing properties

Acute and Subchronic Oral Toxicity Study of Polyherbal Formulation Containing Allium sativum L., Terminalia bellirica (Gaertn.) Roxb., Curcuma aeruginosa Roxb., and Amomum compactum Sol. ex. Maton in Rats

Lack of Reactive Oxygen Species Deteriorates Blood Pressure Regulation in Acute Stress

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Erucin exhibits vasorelaxing effects and antihypertensive activity by H₂S‐releasing properties

Erucin exhibits vasorelaxing effects and antihypertensive activity by H₂S‐releasing properties