Prostacyclin-induced vasodilation in rabbit heart is mediated by ATP-sensitive potassium channels

1993 ◽  
Vol 264 (1) ◽  
pp. H238-H243 ◽  
Author(s):  
W. F. Jackson ◽  
A. Konig ◽  
T. Dambacher ◽  
R. Busse
Keyword(s):  
Nitric Oxide ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Muscle Relaxation ◽  
Rabbit Heart ◽  
Coronary Perfusion Pressure ◽  
Smooth Muscle Relaxation ◽  
Coronary Perfusion ◽  
Langendorff Preparation ◽  
Oxide Synthase

We tested the hypothesis that prostacyclin and its stable analogue iloprost act as agonists of ATP-sensitive potassium channels (KATP) to induce vasodilation of the coronary circulation. The selective blocker of KATP, glibenclamide, was used as a probe for vasodilation mediated by KATP in saline-perfused rabbit hearts (constant flow, Langendorff preparation). Glibenclamide (10-300 nM) significantly increased coronary perfusion pressure and inhibited vasodilation induced by iloprost (1-30 nM), prostacyclin (10 nM), adenosine (0.3 microM), and cromakalim (0.1 microM), a known agonist of KATP. This potassium channel antagonist also inhibited vasodilation of rabbit hearts in response to 10 nM bradykinin in the presence of an inhibitor of nitric oxide synthase (30 microM NG-nitro-L-arginine). Because bradykinin-induced vasodilation is mediated by prostacyclin released from endothelial cells when nitric oxide synthesis is inhibited, these data indicate that glibenclamide is also effective against endogenous prostacyclin. The inhibitory effects of glibenclamide were selective: vasodilation induced by sodium nitroprusside (1-10 microM) or acetylcholine (1 microM) were not inhibited by this potassium channel antagonist. In addition, basal and bradykinin-stimulated release of 6-ketoprostaglandin F1 alpha was not affected by this antagonist of KATP. Glibenclamide also did not inhibit the activation of adenylate cyclase, as indicated by its lack of effect on adenosine 3',5'-cyclic monophosphate accumulation induced by iloprost (10 nM-1 microM) in bovine coronary arterial segments, a tissue in which iloprost-induced vascular smooth muscle relaxation is inhibited by glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Inducible and neuronal nitric oxide synthase involvement in lipopolysaccharide-induced sphincteric dysfunction

2001 ◽  
Vol 280 (1) ◽  
pp. G32-G42 ◽  
Author(s):  
Ya-Ping Fan ◽  
Sushanta Chakder ◽  
Feng Gao ◽  
Satish Rattan
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Muscarinic Agonist ◽  
Basal Tone ◽  
Before And After ◽  
Oxide Synthase ◽  
Nanc Relaxation

We examined the effect of endotoxin lipopolysaccharide (LPS) on the basal tone and on the effects of different stimuli and agonists and transcriptional and translational expression of nitric oxide (NO) synthase (NOS) isozymes in the lower esophageal sphincter (LES), pyloric sphincter (PS), and internal anal sphincter (IAS). NO release was also examined before and after LPS. LPS caused a dose-dependent fall in the basal tone and augmentation of the relaxation caused by nonadrenergic, noncholinergic (NANC) nerve stimulation in the LES and IAS. In the PS, LPS had no significant effect on the basal tone and caused an attenuation of the NANC relaxation and an augmentation of the contractile response of muscarinic agonist. Interestingly, the smooth muscle relaxation by atrial natriuretic factor was suppressed in the LES and IAS but not in the PS. These changes in the sphincteric function following LPS may be associated with increase in the inducible NOS (iNOS) expression since they were blocked by iNOS inhibitorl-canavanine. Augmentation of NANC relaxation in the LES and IAS smooth muscle by LPS may be due to the increased activity of neuronal NOS and NO production.

SIN-1 reverses attenuation of hypercapnic cerebrovasodilation by nitric oxide synthase inhibitors

1994 ◽  
Vol 267 (1) ◽  
pp. R228-R235 ◽  
Author(s):  
C. Iadecola ◽  
F. Zhang ◽  
X. Xu
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Co2 Response ◽  
No Donor ◽  
No Donors ◽  
Doppler Probe ◽  
Nos Inhibitor ◽  
Oxide Synthase

We sought to determine whether the attenuation of the hypercapnic cerebrovasodilation associated with inhibition of nitric oxide synthase (NOS) can be reversed by exogenous NO. Rats were anesthetized (halothane) and ventilated. Neocortical cerebral blood flow (CBF) was monitored by a laser-Doppler probe. The NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg iv) reduced resting CBF [-36 +/- 5% (SE); P < 0.01, analysis of variance] and attenuated the increase in CBF elicited by hypercapnia (partial pressure of CO2 = 50-60 mmHg) by 66% (P < 0.01). L-NAME reduced forebrain NOS catalytic activity by 64 +/- 3% (n = 10; P < 0.001). After L-NAME, intracarotid infusion of the NO donor 3-morpholinosydnonimine (SIN-1; n = 6) increased resting CBF and reestablished the CBF increase elicited by hypercapnia (P > 0.05 from before L-NAME). Similarly, infusion of the guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-bromo-cGMP (n = 6) reversed the L-NAME-induced attenuation of the hypercapnic cerebrovasodilation. The NO-independent vasodilator papaverine (n = 6) increased resting CBF but did not reverse the attenuation of the CO2 response. SIN-1 did not affect the attenuation of the CO2 response induced by indomethacin (n = 6). The observation that NO donors reverse the L-NAME-induced attenuation of the CO2 response suggests that a basal level of NO is required for the vasodilation to occur. The findings are consistent with the hypothesis that NO is not the final mediator of smooth muscle relaxation in hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)

Does potassium channel opening contribute to endothelium-dependent relaxation in human internal thoracic artery?

1999 ◽  
Vol 96 (6) ◽  
pp. 631-638 ◽  
Author(s):  
C. A. HAMILTON ◽  
G. BERG ◽  
K. MCARTHUR ◽  
J. L. REID ◽  
A.F. DOMINICZAK
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Sodium Nitroprusside ◽  
Internal Thoracic Artery ◽  
Channel Blockers ◽  
Channel Opening ◽  
Potassium Channel Blockers ◽  
Oxide Synthase

Opening of potassium channels can cause hyperpolarization and relaxation of vascular smooth muscle cells. The aim of this work was to investigate the contribution of potassium channel activation to vasorelaxation in internal thoracic artery taken from patients undergoing coronary artery bypass graft surgery. Relaxations to carbachol and sodium nitroprusside were studied in isolated rings of internal thoracic artery in the absence and presence of nitric oxide synthase inhibitors and potassium channel blockers. The nitric oxide synthase inhibitors Nω-nitro-⌊-arginine methyl ester and NG-monomethyl-⌊-arginine abolished relaxations to carbachol. Relaxations to both carbachol and sodium nitroprusside were attenuated in the presence of raised extracellular potassium and the potassium channel blockers charybdotoxin, iberiotoxin and tetraethylammonium. Neither apamin nor glibenclamide modified relaxation. ODQ (1H-[1,2,4]oxadiazolol-[4,3a] quinoxalin-1-one), an inhibitor of soluble guanylate cyclase, abolished relaxation to carbachol in rings from some but not all subjects. These results suggest that potassium channel opening may make a small contribution to endothelium-dependent vasorelaxation in internal thoracic artery. The potassium channels had characteristics consistent with those of large-conductance calcium-dependent potassium channels.

Nitric oxide contributes to vascular smooth muscle relaxation in contracting fast-twitch muscles

2001 ◽  
Vol 5 (1) ◽  
pp. 35-44 ◽  
Author(s):  
ROBERT W. GRANGE ◽  
EIJI ISOTANI ◽  
KIM S. LAU ◽  
KRISTINE E. KAMM ◽  
PAUL L. HUANG ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Control Value ◽  
Skeletal Muscle Contraction ◽  
Fast Twitch ◽  
Oxide Synthase

During skeletal muscle contraction, NO derived from neuronal nitric oxide synthase (nNOS) in skeletal muscle fibers or from endothelial cells (eNOS) may relax vascular smooth muscle contributing to functional hyperemia. To examine the relative importance of these pathways, smooth muscle myosin regulatory light chain (smRLC) phosphorylation was assessed as an index of vascular tone in isolated extensor digitorum longus (EDL) muscles from C57, nNOS−/−, and eNOS−/− mice. The smRLC phosphorylation (in mol phosphate per mol smRLC) in C57 resting muscles (0.12 ± 0.04) was increased 3.7-fold (0.44 ± 0.03) by phenylephrine (PE). Reversal of this increase with electrical stimulation (to 0.19 ± 0.03; P < 0.05) was partially blocked by Nω-nitro-l-arginine (NLA). In nNOS−/− EDL, the PE-induced increase in smRLC phosphorylation (0.10 ± 0.02 to 0.49 ± 0.04) was partially decreased by stimulation (0.25 ± 0.04). In eNOS−/− EDL, the control value for smRLC was increased (0.24 ± 0.04), and PE-induced smRLC phosphorylation (0.36 ± 0.06) was decreased by stimulation even in the presence of NLA (to 0.20 ± 0.02; P < 0.05). These results suggest that in addition to NO-independent mechanisms, NO derived from both nNOS and eNOS plays a role in the integrative vascular response of contracting skeletal muscle.

scholarly journals Ropivacaine-Induced Contraction Is Attenuated by Both Endothelial Nitric Oxide and Voltage-Dependent Potassium Channels in Isolated Rat Aortae

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Seong-Ho Ok ◽  
Jeong Yeol Han ◽  
Hui-Jin Sung ◽  
Seong Min Yang ◽  
Jungchul Park ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Barium Chloride ◽  
Enos Phosphorylation ◽  
Voltage Dependent ◽  
Arginine Hydrochloride ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

This study investigated endothelium-derived vasodilators and potassium channels involved in the modulation of ropivacaine-induced contraction. In endothelium-intact rat aortae, ropivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: the nonspecific nitric oxide synthase (NOS) inhibitorNω-nitro-L-arginine methyl ester (L-NAME), the neuronal NOS inhibitorNω-propyl-L-arginine hydrochloride, the inducible NOS inhibitor 1400W dihydrochloride, the nitric oxide-sensitive guanylyl cyclase (GC) inhibitor ODQ, the NOS and GC inhibitor methylene blue, the phosphoinositide-3 kinase inhibitor wortmannin, the cytochrome p450 epoxygenase inhibitor fluconazole, the voltage-dependent potassium channel inhibitor 4-aminopyridine (4-AP), the calcium-activated potassium channel inhibitor tetraethylammonium (TEA), the inward-rectifying potassium channel inhibitor barium chloride, and the ATP-sensitive potassium channel inhibitor glibenclamide. The effect of ropivacaine on endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells was examined by western blotting. Ropivacaine-induced contraction was weaker in endothelium-intact aortae than in endothelium-denuded aortae.L-NAME, ODQ, and methylene blue enhanced ropivacaine-induced contraction, whereas wortmannin,Nω-propyl-L-arginine hydrochloride, 1400W dihydrochloride, and fluconazole had no effect. 4-AP and TEA enhanced ropivacaine-induced contraction; however, barium chloride and glibenclamide had no effect. eNOS phosphorylation was induced by ropivacaine. These results suggest that ropivacaine-induced contraction is attenuated primarily by both endothelial nitric oxide and voltage-dependent potassium channels.

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