OBJECTIVETo review the vasorelaxant effects of hydrogen sulfide (H(2)S) in arterial rings in the cardiovascular system under both physiological and pathophysiological conditions and the possible mechanisms involved.

DATA SOURCESThe data in this review were obtained from Medline and Pubmed sources from 1997 to 2011 using the search terms "hydrogen sulfide" and "vascular relaxation".

STUDY SELECTIONArticles describing the role of hydrogen sulfide in the regulation of vascular activity and its vasorelaxant effects were selected.

RESULTSH(2)S plays an important role in the regulation of cardiovascular tone. The vasomodulatory effects of H(2)S depend on factors including concentration, species and tissue type. The H(2)S donor, sodium hydrosulfide (NaHS), causes vasorelaxation of rat isolated aortic rings in a dose-dependent manner. This effect was more pronounced than that observed in pulmonary arterial rings. The expression of K(ATP) channel proteins and mRNA in the aortic rings was increased compared with pulmonary artery rings. H(2)S is involved in the pathogenesis of a variety of cardiovascular diseases. Downregulation of the endogenous H(2)S pathway is an important factor in the pathogenesis of cardiovascular diseases. The vasorelaxant effects of H(2)S have been shown to be mediated by activation of K(ATP) channels in vascular smooth muscle cells and via the induction of acidification due to activation of the Cl(-)/HCO(3)(-) exchanger. It is speculated that the mechanisms underlying the vasoconstrictive function of H(2)S in the aortic rings involves decreased NO production and inhibition of cAMP accumulation.

CONCLUSIONH(2)S is an important endogenous gasotransmitter in the cardiovascular system and acts as a modulator of vascular tone in the homeostatic regulation of blood pressure.

Animals ; Cardiovascular System ; metabolism ; Humans ; Hydrogen Sulfide ; metabolism ; Vasodilation ; physiology

This study investigated the role of calcium-activated Cl⁻ channels (CaCCs) in mediating vasomotor activity of cerebral basilar artery (BA) of Wistar rat. Pressure myograph was used to examine the changes in diameter of isolated BA to vasoactive reagents. The results showed that (1) The rate of pressure-induced vasomotor activity was 78.6% (n = 28) in BA from 0 to 100 mmHg working pressure. The contractile phase of the response was faster than the relaxation phase; (2) The amplitude of contraction was (62.6 ± 6.4) µm (n = 22), the frequency of contraction was variable and the highest value was 8.0 ± 2.3 per 5 min at 60 mmHg working pressure (n = 22); (3) The pressure-induced vasomotor activity of BA was markedly attenuated when Ca²⁺ was removed from medium; (4) The pressure-induced vasomotor activity was blocked by voltage dependent Ca²⁺ channel blocker nimodipine; (5) The pressure-induced vasomotor was inhibited by CaCC antagonists NFA and NPPB. These results suggest that the pressure-induced vasomotor activity of isolated BA is associated with Ca²⁺ influx that activates CaCCs.
Animals ; Basilar Artery ; physiology ; Calcium ; physiology ; Chloride Channels ; physiology ; Rats ; Rats, Wistar ; Vasoconstriction ; Vasodilation

BACKGROUNDNon-heart-beating donor lung has been a promising source of lung transplantation. Many studies on non-heart-beating donor lungs are based on animal lung transplantation. In this study, we assessed by organ bath the effect of one-hour warm ischemia on the non-heart-beating donor lung in terms of the integrity of contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi.

METHODSSixteen Swedish pigs were randomly classified into two groups: heart-beating donor group and 1-hour warm ischemia non-heart-beating donor group. Pulmonic and bronchial rings were taken from the isolated left lungs of the pigs. The pulmonic rings were stimulated by U-46619 (5.7 mol/L) and acetylcholine (10(-4) mmol/L) to assess the contractile abilities of smooth muscle and the endothelium-dependent relaxation response, respectively. As such, acetylcholine (10(-5) mmol/L) and natrium arachidonic acid (0.01%) were used to detect the contraction of bronchial smooth muscle and epithelium-dependent relaxation response. Meanwhile, the variances of precontraction tension of control groups were recorded to measure whether there was spontaneous relaxation during endothelium/epithelium-dependent relaxation course. Finally, papaverine solution (10(-4) mmol/L) was used to detect the non-endothelium/epithelium-dependent relaxant abilities of pulmonic and bronchial smooth muscles.

RESULTSThere was no significant difference in the tension values of precontraction of pulmonic rings (P > 0.05), endothelium-dependent relaxation (P > 0.05), precontraction of bronchial rings (P > 0.05) and epithelium-dependent relaxation (P > 0.05) between the heart-beating donor group and the 1-hour warm ischemia non-heart-beating donor group. And the pulmonic and bronchial rings of each subgroup B had no spontaneous relaxation. Finally, papaverine solution relaxed the smooth muscle of all the rings completely.

CONCLUSIONSThe results of this experiment suggest that the contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi are not damaged after warm ischemia for 1 hour, and support the further study of non-heart-beating donor lung.

Animals ; Bronchi ; physiology ; Endothelium, Vascular ; physiology ; Lung Transplantation ; Pulmonary Artery ; physiology ; Swine ; Tissue Donors ; Vasodilation ; Warm Ischemia ; methods

Adenosine was identified as a regulator of skeletal muscle blood flow almost 50 years ago. It was first proposed that increased use of ATP during muscle contractions led to net ATP breakdown, and its breakdown product, adenosine, diffused through the interstitial space to the blood stream to be washed away. En-route to its removal, adenosine was suggested to relax the vascular smooth muscle, thereby increasing the blood flow and oxygen supply to the contracting muscle. This mechanism has been researched quite intensively over the years, yet there are still many aspects that remain unclear. It has been confirmed that adenosine does, indeed, relax vascular smooth muscle and contribute to exercise hyperaemia, but the discovery that adenosine was formed extracellularly has shifted the research focus onto its precursor, ATP. ATP is released from many tissues, and produces many effects, including both vasodilation and vasoconstriction, as well as modulation of the neural mechanisms for skeletal muscle blood flow control. This review summarizes the current state of knowledge on the contributions of adenosine and ATP to the skeletal muscle vasodilation that accompanies contractile activity.
Adenosine ; physiology ; Adenosine Triphosphate ; physiology ; Exercise ; physiology ; Hemodynamics ; Humans ; Muscle Contraction ; Muscle, Skeletal ; blood supply ; Muscle, Smooth, Vascular ; physiology ; Regional Blood Flow ; physiology ; Vasoconstriction ; Vasodilation

The purpose of this study was to investigate the vasorelaxing effect and mechanism of idoxifene (a new estrogen receptor modulator) on human internal mammary artery (HIMA). HIMA segments were harvested from men during coronary artery bypass grafting surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, or smoking habit were excluded. The vasorelaxing effect of idoxifene on artery rings from HIMA with and without endothelium was measured by means of perfusion in vitro. Cumulative dose-response to idoxifene in the range of 0.01-10 micromol/L was observed in the presence and absence of NO synthase inhibitor L-NAME. It was also studied whether the vasodilation effect of idoxifene on HIMA was blocked by methylene blue (MB), an inhibitor of guanylate cyclase (GC). The results obtained from idoxifene were compared with those from 17beta-estradiol (E(2)). It was found that idoxifene caused a concentration-dependent relaxation on HIMA. The dose range was from 0.03 micromol/L (minimal vasodilatory concentration) to 3 mmol/L (maximal vasodilatory concentration). It was also found that the vasorelaxation effect of idoxifene on HIMA was dependent on endothelium. E(2) (0.1-100 micromol/L) also resulted in an endothelium-dependent vasorelaxation, but the vessels were 15-fold less sensitive to E(2) than to idoxifene in their vasorelaxation responses. The EC(50) for E(2) was 4.65+/-0.34 micromol/L, compared with 0.32+/-0.02 micromol/L for idoxifene. The mean maximal vasodilatory value of E(2) was 88.3+/-5.7%, compared with 88.6+/-7.2% for idoxifene. Pretreatment with L-NAME (100micromol/L) abolished idoxifene-induced vasodilation virtually by blocking nitric oxide production. The vasorelaxing effect of idoxifene disappeared in the presence of MB (10 micromol/L). These findings demonstrate that idoxifene results in an endothelium-dependent vasorelaxation of HIMA, like estrogen. The effect of idoxifene is more potent than that of traditional estrogen, and is possibly mediated by NO-GC-cGMP pathway.
Estrogen Antagonists ; pharmacology ; Humans ; Mammary Arteries ; drug effects ; physiology ; Tamoxifen ; analogs & derivatives ; pharmacology ; Vasodilation ; drug effects

BACKGROUNDAdiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. The aim of this study was to investigate whether low adiponectin levels predict the impairment of endothelial function in newly diagnosed type 2 diabetic patients in an 8-year prospective study.

METHODSIn the prospective study, we enrolled 133 newly diagnosed type 2 diabetic patients without subclinical atherosclerosis and gave them intensive therapy; the mean treatment period was 8 years. Intensive treatment was a stepwise implementation of behavior modification and pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia and obesity. We measured baseline circulating adiponectin with an enzyme-linked immunosorbent assay, endothelium-dependent and -independent vasodilation by high-resolution vascular ultrasound. At year 8, 102 patients were reexamined for endothelium-dependent and -independent vasodilation.

RESULTSSex-adjusted adiponectin level was positively correlated with endothelium-independent vasodilation both at baseline (r = 0.150, P = 0.043) and at year 8 (r = 0.339, P = 0.001), whereas no association was found between adiponectin and endothelium-dependent vasodilation. In a stepwise multivariate linear regression model, adiponectin was an independent predictor for impaired endothelium-independent vasodilation at year 8 (P = 0.001).

CONCLUSIONSPlasma adiponectin concentration was associated with endothelium-independent vasodilation and hypoadiponectinemia predicted the impairment of endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients under multifactorial intervention. These data support the causative link of impairment of endothelium-independent vasodilation with hypoadiponectinemia.

Adiponectin ; blood ; Diabetes Mellitus, Type 2 ; blood ; physiopathology ; Endothelium, Vascular ; physiology ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Vasodilation ; physiology

Animals ; Aorta, Thoracic ; physiology ; Endothelium ; blood supply ; Male ; Physical Conditioning, Animal ; physiology ; Rats ; Rats, Sprague-Dawley ; Vasodilation

To investigate the effect of peroxynitrite (ONOO(-)) on the reactivity of rabbit pulmonary artery, the responses of rabbit pulmonary artery rings (PARs) pre-incubated with ONOO(-) to endothelium-dependent and receptor-dependent relaxants ACh and ADP, endothelium-dependent and receptor-independent relaxant calcium ionophore A23187, endothelium-independent relaxant sodium nitroprusside (SNP) and alpha(1)-adrenoceptor agonist phenylephrine (PE) were observed in vitro in an accumulative manner. (1) Relaxations of PARs to ACh, calcium ionophore A23187 and ADP were markedly impaired with shift of accumulative dose-response curve of each agonist to the right. Inhibition of endothelium-dependent and receptor-dependent or independent relaxation by ONOO(-) was dose-dependent. (2) ONOO(-) incubation inhibited SNP-induced relaxation in a dose-dependent manner. (3) Contractile response of PARs to PE varied with the different doses of ONOO(-). In PARs pre-incubated with 0.5 mmol/L ONOO(-), contractile response was significantly enhanced with shift of PE accumulative dose-response curve to the left, whereas in PARs pre-incubated with 1.0 mmol/L or 2.0 mmol/L ONOO(-), it was markedly reduced with right shift of PE accumulative dose-response curve. (4) Vehicle of ONOO(-) had no effect on responses to each agonist.Decomposed ONOO(-) had minimal effect on the response to PE and ADP, in contrast, relaxation of PARs to ACh, A23187 and SNP were enhanced. These results indicate that ONOO(-) may contribute to regulatory disorder of pulmonary artery reactivity.
Animals ; Dose-Response Relationship, Drug ; In Vitro Techniques ; Peroxynitrous Acid ; physiology ; Pulmonary Artery ; physiology ; Rabbits ; Vasodilation ; drug effects

Experiments were designed to characterize the cellular mechanisms of action of endothelium-derived vasodilator substances in the rabbit femoral artery. Acetylcholine (ACh, 10(-8)-10(-5) M) induced a concentration-dependent relaxation of isolated endothelium-intact arterial rings precontracted with norepinephrine (NE, 10(-6) M). The ACh-induced response was abolished by the removal of endothelium. NG-nitro-L-arginine (L-NAME, 10(-4) M), an inhibitor of NO synthase, partially inhibited ACh-induced endothelium-dependent relaxation, whereas indomethacin (10(-5) M) showed no effect on ACh-induced relaxation. 25 mM KCl partially inhibited ACh-induced relaxation by shifting the concentration-response curve and abolished the response when combined with L-NAME and NE. In the presence of L-NAME, ACh-induced relaxation was unaffected by glibenclamide (10(-5) M) but significantly reduced by apamin (10(-6) M), and almost completely blocked by tetraethylammonium (TEA, 10(-3) M), iberiotoxin (10(-7) M) and 4-aminopyridine (4-AP, 5 x 10(-3) M). The cytochrome P450 inhibitors, 7-ethoxyresorufin (7-ER, 10(-5) M) and miconazole (10(-5) M) also significantly inhibited ACh-induced relaxation. Ouabain (10(-6) M), an inhibitor of Na+, K(+)-ATPase, or K(+)-free solution, also significantly inhibited ACh-induced relaxation. ACh-induced relaxation was not significantly inhibited by 18-alpha-glycyrrhetinic acid (18 alpha-GA, 10(-4) M). These results of this study indicate that ACh-induced endothelium-dependent relaxation of the rabbit femoral artery occurs via a mechanism that involves activation of Na+, K(+)-ATPase and/or activation of both the voltage-gated K+ channel (Kv) and the large-conductance, Ca(2+)-activated K+ channel (BKCa). The results further suggest that EDHF released by ACh may be a cytochrome P450 product.
Acetylcholine/pharmacology ; Animal ; Biological Factors/physiology* ; Female ; Femoral Artery/physiology* ; Femoral Artery/drug effects ; In Vitro ; Male ; Potassium Channels/physiology* ; Rabbits ; Vasodilation/physiology ; Vasodilator Agents/pharmacology

AIMTo explore the resistant arterial effect of superoxide anion and its possible mechanisms.

METHODSThe third branch of the superior mesenteric artery in male Sprague-Dawley (200-300 g) rats was rapidly excised. Periadventitial fats and connective tissues were removed and the artery was dissected into about 2 mm rings. Each ring was dispensed between two stainless steel wires (diameter 0.0394 mm) in a 5 ml organ bath (DMT 610 M, Danish Myo Technology, Denmark). Isometric force recording studies in vitro of rat mesenteric arterial rings were recorded by Powerlab Syetem. Exposure of arteries to superoxide was accomplished through the auto-oxidation of pyrogallol added to the artery baths. Then endothelium-dependent or independent relaxation was investigated, respectively.

RESULTSExposure to pyrogallol (10, 100, 300, and 1 000 micromol/L) which could produce superoxide anion for 15 min resulted in a dose-dependent manner in a decrease of acetylcholine(ACh)-induced relaxation in rat mesenteric artery. Especially, the two predominant components of acetylcholine(ACh)-induced endothelium-dependent relaxation, EDHF component and NO component were both inhibited by superoxide anion from pyrogallol. However, exposure to superoxide anion from pyrogallol had no effect on the endothelium-independent relaxations to pinacidil or sodium nitroprusside (SNP) in rat mesenteric artery.

CONCLUSIONThese results indicate that superoxide anion can inhibit the endothelium-dependent relaxation in rat mesenteric artery, but has no effect on the endothelium-independent relaxation, in which the inhibited effect of EDHF and NO from endothelium is involved.

Acetylcholine ; pharmacology ; Animals ; Endothelium-Dependent Relaxing Factors ; physiology ; In Vitro Techniques ; Male ; Mesenteric Arteries ; physiology ; Nitric Oxide ; physiology ; Rats ; Rats, Sprague-Dawley ; Superoxides ; pharmacology ; Vasodilation ; physiology