Effects of sulfhydryl reagents on nitroglycerin-induced relaxation of bovine coronary artery

1986 ◽  
Vol 64 (11) ◽  
pp. 1395-1401 ◽  
Author(s):  
Carl A. Gruetter ◽  
Sally M. Lemke
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Vascular Smooth Muscle ◽  
Guanylate Cyclase ◽  
Ethacrynic Acid ◽  
Muscle Relaxation ◽  
Alkylating Agents ◽  
Sulfhydryl Groups ◽  
Smooth Muscle Relaxation

The mechanism whereby nitroglycerin relaxes vascular smooth muscle remains uncertain. A current hypothesis suggests that nitroglycerin reacts with critical cellular sulfhydryl groups to form an intermediate, which activates guanylate cyclase, resulting in cGMP accumulation and relaxation. This study investigated further the potential involvement of sulfhydryls in nitroglycerin-induced vascular smooth muscle relaxation by evaluating effects of a variety of sulfhydryl alkylating and reducing agents on responses to nitroglycerin and other relaxants in bovine coronary arterial strips submaximally contracted using 30 mM K. Whereas 10−4 M 5,5′-dithiobis-(2-nitrobenzoicacid), 10−5M N-ethylmaleimide, and 10−4M N-naphthylmaleimide did not affect nitroglycerin-induced relaxation, 10−4 M N-ethylmaleimide and 10−4 M ethacrynic acid significantly inhibited relaxation induced by nitroglycerin. Both ethacrynic acid and N-ethylmaleimide at 10−4 M also inhibited relaxation induced by sodium nitroprus-side. N-ethylmaleimide, but not ethacrynic acid, inhibited relaxation induced by isoproterenol and forskolin. Ethacrynic acid significantly reduced both relaxation and cGMP elevation induced by both 10−7 M nitroglycerin and 10−7 M sodium nitroprusside. Ethacrynic acid, but not N-ethylmaleimide, significantly reduced relaxation induced by 8-Br-cGMP. Pretreatment with the sulfhydryl-containing agents N-acetylcysteine, 2-mercaptoethanol, or dithiothreitol, at 10−3 M did not affect nitroglycerin-induced relaxation in nontolerant arteries. Similarly, N-acetylcysteine and dithiothreitol did not alter the depressed responses to nitroglycerin in arteries in which tolerance to nitroglycerin was induced in vitro. A slight but statistically significant reversal of nitroglycerin-tolerance occurred after treatment of tolerant arteries with 2-mercaptoethanol. As none of the sulfhydryl alkylating agents tested inhibited selectively nitroglycerin-induced relaxation, and none of the sulfhydryl-containing agents markedly enhanced nitroglycerin-induced relaxation in either nontolerant or tolerant arteries, the results provide little evidence to support the hypothesis that critical sulfhydryl groups are involved specifically in nitroglycerin-induced relaxation of arterial smooth muscle. The results do suggest that ethacrynic acid may selectively inhibit relaxation induced in bovine coronary artery by relaxants that act by activating guanylate cyclase, and that the inhibition by ethacrynic acid may involve two mechanisms, an inhibition of guanylate cyclase activation and an inhibition of the relaxant effect of cGMP.

scholarly journals EVALUATION OF IN-VITRO VASORELAXANT EFFECT (POTENTIAL ANTIHYPERTENSIVE) OF KIGELIA AFRICANA FRUIT METHANOL EXTRACT ON POTASSIUM CHLORIDE AND PHENYLEPHRINE INDUCED TENSION IN WISTAR RAT AORTA

2020 ◽  
Vol 4 (3) ◽  
pp. 470-475
Author(s):  
A. O. Isah ◽  
M. Idu ◽  
A. A. Abdulrahman ◽  
F. Amaechina
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Potassium Chloride ◽  
Methanol Extract ◽  
Muscle Relaxation ◽  
Rat Aorta ◽  
Smooth Muscle Relaxation ◽  
Organ Bath ◽  
Vasorelaxant Effect

This research on Kigelia africana was conducted in order to ascertain its ability to relax excited vascular smooth muscle in rat aorta. Preliminary investigation on whether the plant exhibits antihypertensive property was done before the evaluation of in vitro vasorelaxant effect. The vasorelaxant activity was determined using in vitro method on rat aorta with the aid of perfusion apparatus with a detachable organ bath. The administration of potassium chloride (KCl) raised the tension from 1.0 to 1.31 indicating that the aorta got to its peak of contraction. At 10 and 20mg/kg, the tension dropped significantly, showing relaxation of the smooth muscle while at 5mg/kg, drop in tension was insignificant at p˂0.05. However, at some of the doses, towards the end of experiment, there was steady resurge in tension showing that the aorta resumed contraction. On the application of phenylephrine (PE), the tension rose to 1.18g. On administration of the extract, the tension dropped slightly showing mild vascular smooth muscle relaxation. From the results obtained, there was seeming similarity in the action of the K. africana compared to amlodipine/Ramipril in KCl and PE induced tension in aorta respectively. However, at 10 and 20mg/kg, a substantial decrease in tension was noted indicating that the extract action is dose dependent. Thus, from this in-vitro smooth muscle relaxation study in rats, the methanol extract of K. africana has depressant property that was likely expressed by enhancing the closing of voltage operated calcium channel and ACE inhibiting activity in KCl and Phenylephrine induced tension respectively.

scholarly journals Arteriolar vasodilation involves actin depolymerization

2018 ◽  
Vol 315 (2) ◽  
pp. H423-H428
Author(s):  
Philip S. Clifford ◽  
Brian S. Ferguson ◽  
Jeffrey L. Jasperse ◽  
Michael A. Hill
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Muscle Relaxation ◽  
Nitric Oxide Donor ◽  
Smooth Muscle Relaxation ◽  
Myosin Light Chain Phosphorylation ◽  
Actin Depolymerization

It is generally assumed that relaxation of arteriolar vascular smooth muscle occurs through hyperpolarization of the cell membrane, reduction in intracellular Ca2+ concentration, and activation of myosin light chain phosphatase/inactivation of myosin light chain kinase. We hypothesized that vasodilation is related to depolymerization of F-actin. Cremaster muscles were dissected in rats under pentobarbital sodium anesthesia (50 mg/kg). First-order arterioles were dissected, cannulated on glass micropipettes, pressurized, and warmed to 34°C. Internal diameter was monitored with an electronic video caliper. The concentration of G-actin was determined in flash-frozen intact segments of arterioles by ultracentrifugation and Western blot analyses. Arterioles dilated by ~40% of initial diameter in response to pinacidil (1 × 10−6 mM) and sodium nitroprusside (5 × 10−5 mM). The G-actin-to-smooth muscle 22α ratio was 0.67 ± 0.09 in arterioles with myogenic tone and increased significantly to 1.32 ± 0.34 ( P < 0.01) when arterioles were dilated with pinacidil and 1.14 ± 0.18 ( P < 0.01) with sodium nitroprusside, indicating actin depolymerization. Compared with control vessels (49 ± 5%), the percentage of phosphorylated myosin light chain was significantly reduced by pinacidil (24 ± 2%, P < 0.01) but not sodium nitroprusside (42 ± 4%). These findings suggest that actin depolymerization is an important mechanism for vasodilation of resistance arterioles to external agonists. Furthermore, pinacidil produces smooth muscle relaxation via both decreases in myosin light chain phosphorylation and actin depolymerization, whereas sodium nitroprusside produces smooth muscle relaxation primarily via actin depolymerization. NEW & NOTEWORTHY This article adds to the accumulating evidence on the contribution of the actin cytoskeleton to the regulation of vascular smooth muscle tone in resistance arterioles. Actin depolymerization appears to be an important mechanism for vasodilation of resistance arterioles to pharmacological agonists. Dilation to the K+ channel opener pinacidil is produced by decreases in myosin light chain phosphorylation and actin depolymerization, whereas dilation to the nitric oxide donor sodium nitroprusside occurs primarily via actin depolymerization. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/vascular-smooth-muscle-actin-depolymerization/ .

Modulation of vascular tone by neutrophils: dependence on endothelial integrity

1989 ◽  
Vol 257 (4) ◽  
pp. H1315-H1320
Author(s):  
J. L. Mehta ◽  
D. L. Lawson ◽  
W. W. Nichols ◽  
P. Mehta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxant ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Smooth Muscle Tone ◽  
High Concentrations ◽  
Vascular Smooth Muscle Tone ◽  
Smooth Muscle Relaxant

To determine the influence of polymorphonuclear leukocytes (PMNLs) on vascular smooth muscle tone, isolated human PMNLs (10(4)–10(7) cells/ml) were suspended in a tissue bath with precontracted rat aortic rings with or without endothelium. PMNLs in low concentrations (10(4) and 10(5) cells/ml) caused a mild contraction, and in higher concentrations (10(6) and 10(7) cells/ml) caused a modest relaxation of aortic rings with intact endothelium. In contrast, PMNLs caused a potent concentration-dependent relaxation of deendothelialized rings (P less than 0.01 compared with rings with intact endothelium). The PMNL-induced vascular smooth muscle relaxation was abolished by both hemoglobin and methylene blue and potentiated by both superoxide dismutase and captopril. Although suspension of PMNLs caused release of eicosanoids, thromboxane A2 and prostacyclin, from rings with intact endothelium, neither indomethacin nor the TxA2-endoperoxide receptor antagonist SQ 29548 modified the effects of PMNLs on vascular smooth muscle tone. These observations suggest that unstimulated PMNLs generate a smooth muscle relaxant, which has biological characteristics similar to the endothelium-derived relaxing factor. Since the activity of this PMNL-derived smooth muscle relaxant is more pronounced in deendothelialized vascular segments, it appears that endothelium provides a barrier against vasorelaxation by high concentrations of PMNLs.

Interactions between nitroglycerin and endothelium in vascular smooth muscle relaxation

1991 ◽  
Vol 260 (3) ◽  
pp. H698-H701 ◽  
Author(s):  
J. L. Dinerman ◽  
D. L. Lawson ◽  
J. L. Mehta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Cyclic Monophosphate ◽  
The Mean ◽  
Smooth Muscle Relaxant ◽  
Vascular Smooth Muscle Relaxation

To evaluate the role of endothelium in nitroglycerin (NTG)-mediated vascular relaxation, epinephrine-contracted rat thoracic aortic segments with and without intact endothelium were exposed to NTG (10(-10) to 10(-5) M). Aortic segments with intact (endo+, n = 15) and denuded endothelium (endo-, n = 9) exhibited typical NTG-induced relaxation. However, the mean effective concentration of NTG was lower for endo- than for endo+ segments (P less than 0.001). To determine if this phenomenon related to nitric oxide (NO) generation by endothelium, six endo+ segments were treated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO production. These endo+ segments exhibited greater (P less than 0.001) relaxation in response to NTG than the untreated endo+ segments. Oxyhemoglobin, an inhibitor of guanylate cyclase activation, greatly diminished NTG-mediated relaxation of all aortic segments. To determine if the enhanced NTG-mediated relaxation of endo- segments was unique to the guanosine 3',5'-cyclic monophosphate-dependent vasodilator NTG, other endo+ and endo- segments were exposed to adenosine 3',5'-cyclic monophosphate-dependent vasodilator papaverine (10(-8) to 10(-4) M), and no difference in EC50 was noted between endo+ and endo- segments. Thus endothelium attenuates NTG-mediated vasorelaxation, and this attenuation is abolished by inhibition of endothelial NO production with L-NMMA. These observations indicate that endothelium is a dynamic modulator of vascular smooth muscle relaxant effects of NTG. This modulation appears to result from a competitive interaction between endothelial NO and NTG.

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