nitroarginine and alpha-beta-methyleneadenosine-5--triphosphate

Our knowledge of the effects of P2-receptor activation on renal vascular tone comes mostly from in vitro models. We aimed to characterise the pharmacology of ATP in the renal circulation in vivo.. In pentobarbitone anaesthetized rabbits, we examined total renal and medullary vascular responses to ATP (0.2 and 0.8 mg kg(-1)), beta, gamma-methylene ATP (beta, gamma-mATP, 7 and 170 microg kg(-1)), alpha, beta-mATP (0.2 and 2 microg kg(-1)) and adenosine (2 and 6 microg kg(-1)) using transit-time ultrasound and laser Doppler flowmetry, respectively. We also determined whether adenosine receptors, NO or prostanoids contribute to the actions of the purinoceptor agonists.. Renal arterial boluses of ATP, beta,gamma-mATP, and adenosine produced biphasic changes; ischaemia followed by hyperaemia, in total renal and medullary blood flow. alpha,beta-mATP induced only ischaemia. The adenosine receptor antagonist 8-(p-sulphophenyl)theophylline reduced the responses to adenosine and the hyperaemic responses to ATP and beta,gamma-mATP only. NO synthase inhibition (Nomega-nitro-L-arginine) did not significantly alter responses to the P2 receptor agonists. Subsequent cyclooxygenase inhibition (ibuprofen) reduced the ATP- and beta, gamma-mATP-induced increases in renal blood flow. All other responses remained unchanged.. In the rabbit kidney in vivo, alpha, beta-mATP sensitive receptors mediate vasoconstriction. beta,gamma-mATP and ATP induce vasodilation at least partly through adenosine receptors. ATP induced renal vasodilatation is independent of NO and partly dependent on prostanoids in the bulk of the kidney, but not in the vasculature controlling medullary blood flow.

Topics: Adenosine; Adenosine Triphosphate; Animals; Cyclooxygenase Inhibitors; Ibuprofen; Kidney; Kidney Cortex; Kidney Medulla; Laser-Doppler Flowmetry; Male; Nitric Oxide Synthase; Nitroarginine; Prostaglandins; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Rabbits; Receptors, Purinergic P1; Receptors, Purinergic P2; Regional Blood Flow; Renal Circulation; Theophylline

1. Conflicting views exist on whether ATP is a neurotransmitter in the enteric nervous system. We investigated the role of ATP in enteric transmission in circular muscle strips of the mouse jejunum. 2. On PGF2alpha-precontracted muscle strips and in the presence of atropine and guanethidine, electrical field stimulation (EFS, 1-8 Hz) of nonadrenergic noncholinergic (NANC) nerves induced transient relaxations that were abolished by the nerve-conductance blocker tetrodotoxin. The NO synthase blocker l-nitroarginine (l-NOARG) partially inhibited the NANC relaxations to EFS, but fast-twitch relaxations to EFS were still observed in the presence of l-NOARG. 3. In the presence of l-NOARG, ATP, the P2X receptor agonist alphabetaMeATP and the P2Y receptor agonist ADPbetaS relaxed jejunal muscle strips. Tetrodotoxin did not affect the relaxation to ATP and ADPbetaS, but inhibited that to alphabetaMeATP. 4. The l-NOARG-resistant NANC relaxations to EFS were almost abolished by apamin, a blocker of small-conductance Ca2+ activated K+ channels, and by suramin and PPADS, blockers of P2 purinoceptors. Relaxations to ATP were almost abolished by apamin and suramin but not affected by PPADS. 5. Desensitisation of alphabetaMeATP-sensitive P2X receptors, the P2X receptor blocker Evans blue and the P2X1,2,3 receptor blocker NF 279 inhibited the l-NOARG-resistant NANC relaxations to EFS and that to alphabetaMeATP without affecting the relaxation to ADPbetaS. Brilliant blue G, a P2X2,5,7 receptor blocker, did not affect the relaxations to EFS. 6. Desensitisation of P2Y receptors and MRS 2179, a P2Y1 receptor blocker, virtually abolished the l-NOARG-resistant NANC relaxations to EFS and the relaxation to ADPbetaS without affecting the relaxation to alphabetaMeATP. 7. Dipyridamole, an adenosine uptake inhibitor, or theophylline and 8-phenyltheophylline, blockers of P1 and A1 purinoceptors, respectively, did not affect the purinergic NANC relaxations to EFS. 8. Our results suggest that ATP or a related purine acts as an inhibitory NANC neurotransmitter in the mouse jejunum, activating P2 but not P1 purinoceptors. Relaxations to the purinergic NANC neurotransmitter mainly involve P2Y receptors of the P2Y1 subtype that are located postjunctionally. Purinergic NANC neurotransmission also involves P2X receptors, most likely of the P2X1 and P2X3 subtype, located pre- and/or postjunctionally.

Topics: Adenosine Triphosphate; Animals; Apamin; Electric Stimulation; Enzyme Inhibitors; In Vitro Techniques; Jejunum; Mice; Muscle Relaxation; Muscle, Smooth; Neurotransmitter Agents; Nitric Oxide Synthase; Nitroarginine; Protein Isoforms; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Pyridoxal Phosphate; Receptors, Purinergic P2; Suramin; Synaptic Transmission; Thionucleotides

Bradykinin evokes endothelium-dependent relaxation in some vascular beds; on the other hand, the possibility has been demonstrated that in certain organs, such as the adrenal medulla or atria, bradykinin may enhance transmitter release from the sympathetic nerves. We hypothesized that bradykinin may also enhance postganglionic sympathetic neurotransmission in blood vessels. To test this hypothesis, we recorded excitatory junction potentials (EJPs), a measure of sympathetic purinergic neurotransmission, in rat mesenteric resistance arteries with a conventional microelectrode technique. EJPs were elicited by repetitive perivascular nerve stimulation (1 Hz, 20 to 50 V, 30 to 60 micros, 11 pulses). In this preparation, bradykinin (10(-7) or 10(-6) mol/L) significantly enhanced the amplitude of EJPs without altering the resting membrane potential. This effect of bradykinin was blocked by Hoe 140, a bradykinin B2 receptor antagonist, but not by des-Arg(9),[Leu(8)]-bradykinin, a bradykinin B1 receptor antagonist. The cyclooxygenase inhibitor indomethacin or NO synthase inhibitor N(G)-nitro-L-arginine did not alter the effect of bradykinin. Captopril, an ACE inhibitor, but not candesartan, an angiotensin II type 1 receptor antagonist, enhanced the action of a low concentration (10(-8) mol/L) of bradykinin on EJPs. These findings suggest that in rat mesenteric resistance arteries, bradykinin enhances sympathetic purinergic neurotransmission, presumably through presynaptic bradykinin B2 receptors. The clinical relevance of the present findings remains unclear; however, the fact that the ACE inhibitor, but not the angiotensin II type 1 receptor antagonist, enhanced the action of bradykinin on sympathetic neurotransmission may warrant further investigation.

Topics: Adenosine Triphosphate; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzimidazoles; Biphenyl Compounds; Bradykinin; Captopril; Cyclooxygenase Inhibitors; Drug Interactions; Excitatory Postsynaptic Potentials; In Vitro Techniques; Indomethacin; Male; Membrane Potentials; Mesenteric Arteries; Microelectrodes; Neuromuscular Junction; Nitric Oxide Synthase; Nitroarginine; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Stimulation, Chemical; Sympathetic Nervous System; Synaptic Transmission; Tetrazoles

Changes in bronchial vascular tone, in part due to cooling during ventilation, may contribute to altered control of airflow during airway inflammation, asthma, and exercise-induced bronchoconstriction. We investigated the responses of canine bronchial vasculature to excitatory stimuli and cooling. Electrical stimulation evoked contractions in only some (8 of 88) tissues; these were phentolamine sensitive and augmented by N(omega)-nitro-L-arginine. However, sustained contractions were evoked in all tissues by phenylephrine [concentration evoking a half-maximal response (EC(50)) approximately 2 microM] or the thromboxane A(2) mimetic U-46619 (EC(50) approximately 5 nM) and less so by beta,gamma-methylene-ATP or histamine. Cooling to room temperature markedly suppressed ( approximately 75%) adrenergic responses but had no significant effect against U-46619 responses. Adrenergic responses, but not those to U-46619, were accompanied by an increase in intracellular Ca(2+) concentration. Chelerythrine (protein kinase C antagonist) markedly antagonized adrenergic responses (mean maxima reduced 39% in artery and 86% in vein) but had no significant effect against U-46619, whereas genistein (a nonspecific tyrosine kinase inhibitor) essentially abolished responses to both agonists. We conclude that cooling of the airway wall dramatically interferes with adrenergic control of bronchial perfusion but has little effect on thromboxane-mediated vasoconstriction.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine Triphosphate; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchi; Bronchial Arteries; Calcium; Cold Temperature; Dogs; Dose-Response Relationship, Drug; Electric Stimulation; Enzyme Inhibitors; Genistein; In Vitro Techniques; Nitroarginine; Phentolamine; Protein Kinase C; Protein-Tyrosine Kinases; Trachea; Vasoconstriction; Vasoconstrictor Agents; Veins

Diadenosine tetraphosphate (AP4A) can be released from activated platelets and the present study examined its effect on coronary arterial microvessels. The role of purinoceptors in the coronary microcirculation in vivo was also investigated. In open chest dogs, coronary arterioles were observed using a microscope with a floating objective. In Protocol 1, AP4A (1, 10, 100 and 1,000 micromol/L) was superfused onto the heart surface before and during the superfusion of 10 micromol/L of 8-phenyltheophylline (8-PT), a P1 purinoceptor blocker. In Protocol 2, AP4A (0.1, 1, 10, and 100 nmol x kg(-1) x min(-1)) was infused into the left anterior descending coronary artery before and during the superfusion of 10 micromol/L of 8-PT. In addition to 8-PT, 30 micromol/L of pyridoxalphosphate-6-azophenyl 2',4'-disulphonic acid (PPADS), a P2X purinoceptor blocker in Protocol 3, or 300 micromol/L of N(omega)-nitro-L-arginine (LNNA) in Protocol 4, was continuously superfused, and 4 doses of AP4A were cumulatively superfused as in Protocol 1. In Protocol 5, 10 micromol/L of alpha,beta-methylene ATP, an agonist of P2X purinoceptors, was superfused for 60 min. Superfused AP4A dilated arterioles in a dose-dependent manner. The magnitude of dilatation was greater in smaller arterioles (small vessel < or = 150 microm: 24.5+/-2.2% vs large vessel > 150 microm: 10.6+/-1.5% at a dose of 1,000 micromol/L, p<0.001). On the other hand, intraluminally applied AP4A also dilated arterioles, but no size dependency was shown. In the presence of 8-PT, vasodilatory responses to superfused and intraluminally applied AP4A were attenuated and the lower doses of AP4A constricted arterioles. This vasoconstrictor effect was not affected by PPADS. The vasodilatory effect of the higher doses of AP4A was almost abolished in the presence of LNNA. Alpha,beta-methylene ATP had no effect on coronary microvascular diameters. AP4A has bidirectional effects on coronary arterial microvessels: vasodilatory effects mediated by P1 purinoceptors and NO, which might be mediated by P2Y purinoceptors, and a vasoconstrictor effect, which is not mediated by P2X purinoceptors.

Topics: Adenosine Triphosphate; Animals; Arterioles; Coronary Circulation; Coronary Vessels; Dinucleoside Phosphates; Dogs; Female; Fluorescein Angiography; Male; Microcirculation; Nitric Oxide; Nitroarginine; Nitroprusside; Receptors, Purinergic P1; Receptors, Purinergic P2; Theophylline; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

The effects of P2Y receptor agonists on smooth muscle membrane potential in isolated ring segments of rat mesenteric artery were examined by intracellular microelectrodes. In the presence of inhibitors of nitric oxide-synthase and cyclo-oxygenase, the selective P2Y1 receptor agonist adenosine 5'-O-thiodiphosphate (ADPbetaS) induced endothelium-dependent membrane hyperpolarisations, which were abolished by a combination of the K+ channel inhibitors charybdotoxin and apamin, providing direct evidence that ADPbetaS releases endothelium-derived hyperpolarising factor (EDHF). 2-MethylthioATP and ATP, each which stimulates both endothelial P2Y receptors and P2X receptors on the smooth muscle cells, also elicited hyperpolarisation, but only after desensitisation of P2X receptors with alphabeta-methylATP indicating that simultaneous activation of P2X receptors may counteract the action of EDHF. In conclusion, activation of endothelial P2Y receptors induce release of EDHF.

Topics: Acetylcholine; Adenosine Diphosphate; Adenosine Triphosphate; Animals; Biological Factors; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Female; In Vitro Techniques; Indomethacin; Membrane Potentials; Mesenteric Arteries; Muscle Relaxation; Muscle, Smooth, Vascular; Nitroarginine; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2; Thionucleotides; Vasodilation; Vasodilator Agents

Aims of this study were to functionally and histologically determine the localization of ganglia that distribute inhibitory nerves to the penile corpus cavernosum in dogs. In isolated corpus cavernosa from seven control dogs contracted with endothelin-1, transmural electrical stimulation (5 Hz for 40 s) elicited contractions which were reversed to relaxations by prazosin. The relaxation was abolished by NG-nitro-l-arginine (l-NNA), a nitric oxide (NO) synthase inhibitor, and restored by l-arginine. Parts of bilateral pelvic nerve plexuses running to the penis were surgically denervated in anesthetized three dogs, or the bilateral neuronal tissues close to the corpus cavernosum were removed for denervation in seven dogs. One week after the operation, the dogs were sacrificed. Denervation of pelvic plexus did not attenuate neurogenic relaxations, whereas denervation of the distal portion abolished the responses. In the tissues close to the corpus cavernosum excised for denervation, ganglia containing abundant nerve cells and fibers stained by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase method were histochemically detected. One week after the denervation, there were no NADPH diaphorase-positive nerve fibers in the trabecula of corpus cavernosum. It is concluded that neurogenic relaxations of canine corpus cavernosum are mediated by NO synthesized from l-arginine in nerve terminals, and this nerve is originated from ganglia located close to the corpus cavernosum but not directly from the pelvic nerve plexus.

Topics: Adenosine Triphosphate; Animals; Denervation; Dogs; Dose-Response Relationship, Drug; Electric Stimulation; Male; NADPH Dehydrogenase; Nerve Fibers; Neural Inhibition; Nicotine; Nicotinic Agonists; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Penis; Prazosin; Stimulation, Chemical; Sympatholytics; Tetrodotoxin

To determine the involvement of noradrenergic and other vasoconstrictor nerves in the contraction of ocular arteries and the modification by cholinergic and nitroxidergic nerves of vasoconstrictor nerve function.. Changes in isometric tension were recorded in helical strips of the canine posterior ciliary and external ophthalmic arteries denuded of the endothelium, which were stimulated by transmurally applied electrical pulses (5 Hz). Vasoconstrictor mediators were analyzed by pharmacological antagonists, such as prazosin, alpha,beta-methylene ATP, a P2alpha-purinoceptor antagonist, and BIBP3226, a neuropeptide Y receptor antagonist.. Transmural electrical stimulation produced contractions that were potentiated by N(G)-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor. The contraction was partially inhibited by prazosin and abolished by combined treatment with alpha,beta-methylene ATP but was not influenced by BIBP3226. Stimulation-induced contraction was attenuated by physostigmine and potentiated by atropine. Contractions induced by exogenous ATP were reversed to relaxations by alpha,beta-methylene ATP. In the strips treated with L-NA, prazosin, and alpha,beta-methylene ATP, the addition of L-arginine elicited relaxations by nerve stimulation. The ATP-induced relaxation was attenuated by aminophylline, whereas neurogenic relaxation was unaffected.. Ciliary and ophthalmic arterial contractions by nerve stimulation are mediated by norepinephrine and ATP, which stimulate alpha1-adrenoceptor and P2X purinoceptor, respectively. ATP from the nerve is unlikely involved in vasodilatation. Acetylcholine derived from the nerve impairs the neurogenic contraction, possibly by interfering with the release of vasoconstrictor transmitters, and neurogenic NO also inhibits the contraction postjunctionally by physiological antagonism.

Topics: Acetylcholine; Adenosine Triphosphate; Adrenergic alpha-Antagonists; Animals; Autonomic Nervous System; Cholinergic Fibers; Ciliary Arteries; Dogs; Electric Stimulation; Female; Isometric Contraction; Male; Muscle, Smooth, Vascular; Nitric Oxide; Nitroarginine; Norepinephrine; Ophthalmic Artery; Receptors, Adrenergic, alpha-1; Receptors, Neuropeptide Y; Receptors, Purinergic P2; Vasoconstriction

In isolated monkey lingual arteries denuded of the endothelium and contracted with prostaglandin F2alpha, transmural electrical stimulation produced a contraction that was reduced by prazosin and reversed to a relaxation by additional treatment with alpha,beta-methylene ATP. The relaxation thus induced was abolished by tetrodotoxin and N(G)-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and L- but not D-arginine restored the response in the L-NNA-treated arteries. Under treatment with prazosin and alpha,beta-methylene ATP, the arterial strips responded to nicotine with a relaxation that was not influenced by atropine and timolol but was abolished by hexamethonium, oxyhemoglobin, and methylene blue. The nicotine-induced relaxation was abolished by L-NNA but not by N(G)-nitro-D-arginine and was reversed by L-arginine. Relaxations to exogenously applied NO (acidified NaNO2 solution) were not influenced by L-NNA but were abolished by oxyhemoglobin and methylene blue. The response was not affected in the strips made unresponsive to vasoactive intestinal polypeptide and calcitonin gene-related peptide by desensitization. Histochemical study demonstrated the presence of perivascular neurons containing neuronal NO synthase. It is concluded that monkey lingual arteries are innervated by vasoconstrictor nerves liberating norepinephrine and possibly ATP and also by nonadrenergic noncholinergic vasodilator nerves liberating NO as a neurotransmitter to activate soluble guanylate cyclase. Vasoactive intestinal polypeptide and calcitonin gene-related peptide do not appear to be involved in the neurogenic vasodilatation.

Topics: Adenosine Triphosphate; Animals; Arteries; Dinoprost; Electric Stimulation; Female; In Vitro Techniques; Macaca; Male; Muscle, Smooth, Vascular; Nerve Fibers; Neurons; Nicotine; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Prazosin; Stereoisomerism; Tongue; Vasodilation

1. Neurogenic responses to transmural electrical stimulation were examined in endothelium-denuded extrameningeal (vertebral and carotid) and intrameningeal (spinal, basilar and middle cerebral) arteries isolated from dogs. 2. In the extrameningeal arteries, transmural electrical stimulation produced a phasic contraction. This contraction was abolished by tetrodotoxin, prazosin and guanethidine. However, alpha,beta-methylene ATP and NG-nitro-L-arginine (L-NOARG) had no significant effect on the contractile responses. 3. In the intrameningeal arteries, the neurogenic responses to electrical stimulation were composed of a transient contraction and relaxation. The transient contraction was selectively inhibited by guanethidine L-NOARG abolished the relaxation but not the contraction induced by electrical stimulation. Prazosin had no effect on either neurogenic response. 4. Noradrenaline produced a large contraction in the extrameningeal arteries which was selectively inhibited by prazosin. alpha,beta-Methylene ATP produced neither contraction nor inhibition of the response to noradrenaline in the extrameningeal arteries. 5. In the intrameningeal arteries, alpha,beta-methylene ATP produced a greater contraction than noradrenaline. The response to alpha,beta-methylene ATP was selectively abolished by desensitization of P2x-purinoceptors with alpha,beta-methylene ATP itself. The contractile response to noradrenaline was inhibited by rauwolscine but not by prazosin. 6. ATP produced endothelium-dependent relaxations in the extrameningeal and intrameningeal arteries, which were attenuated by endothelium removal. 7. NADPH diaphorase-positive fibres were dense in the middle cerebral and basilar arteries but rare or absent in the spinal artery. In the extrameningeal arteries diaphorase-positive traces were observed in the vasa vasorum. 8. The present findings indicate that the neurogenic responses of intrameningeal arteries of dogs are composed of NO-ergic and sympathetic purinergic components, while the extrameningeal arteries tested produced only sympathetic adrenergic responses, suggesting that regional heterogeneity may be associated with a sudden transition in innervation and receptor expression at the meninx.

Topics: Adenosine Triphosphate; Adrenergic alpha-Agonists; Animals; Arginine; Arteries; Basilar Artery; Carotid Arteries; Cerebral Arteries; Dogs; Electric Stimulation; Endothelium, Vascular; Female; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth, Vascular; NADPH Dehydrogenase; Nerve Fibers; Nitroarginine; Norepinephrine; Vertebral Artery

The participation of nitric oxide in the relaxation of the cat lower esophageal sphincter muscle strip in response to electrical field stimulation or administration of nicotine was studied. The nicotine-induced relaxation was mediated via a neuronal pathway, since it was inhibited by administration of hexamethonium or tetrodotoxin. Inhibition of nitric oxide biosynthesis by N-nitro-L-arginine decreased the relaxation induced by nicotine (50 microM) or field stimulation. With the maximal concentration of N-nitro-L-arginine (1 mM) electrical field stimulation-induced relaxation was abolished, while nicotine-induced relaxation decreased by 70%. L-Arginine (1 mM) partly restored this relaxation. Desensitization of P2x receptors by alpha, beta methylene-adenosine 5-triphosphate (alpha, beta-m-ATP) did not change the relaxation induced by either electrical field stimulation or administration of nicotine. It is therefore suggested that the field stimulation-induced relaxation is mediated by the release of nitric oxide, but in the nicotine-produced relaxation is only partly due to nitric oxide, other factor(s) might be also be involved.

Topics: Adenosine Triphosphate; Animals; Arginine; Cats; Electric Stimulation; Esophagogastric Junction; In Vitro Techniques; Muscle Relaxation; Nicotine; Nitric Oxide; Nitroarginine

1. Responses of the carotid artery of rabbits to intraluminal and abluminal administration of purinergic agonists were examined. The carotid artery was perfused in vitro and changes in diameter were recorded. 2. Intraluminal acetylcholine, ADP, and ATP produced pronounced vasodilatation, whereas abluminal acetylcholine, but not ADP and ATP, produced dilatation of phenylephrine-preconstricted arteries. Intra- and abluminal adenosine and nitroprusside produced equipotent vasodilatation. 3. N omega-nitro-L-arginine abolished dilator responses to acetylcholine and adenine nucleotides, and unmasked vasoconstrictor responses to high concentrations of these agonists. Responses to adenosine and nitroprusside were not affected by nitro-L-arginine. 4. Intraluminal, but not abluminal, administration of nucleotidase-resistant adenine nucleotide analogues 2-methylthio-ATP and ADP beta S produced significant vasodilation in arteries preconstricted with phenylephrine. Intra- and abluminal administration of alpha,beta-methylene-ATP, a potent P2X-purinoceptor agonist, did not produce vasodilatation in preconstricted arteries. 5. Abluminal ADP failed to elicit dilatation of phenylephrine-preconstricted arteries even in the presence of the ADPase inhibitor beta,gamma-methylene-ATP (10(-5)M). When P2X-purinoceptors, which mediate adenine nucleotide-induced vasoconstriction, were stimulated with alpha,beta-methylene-ATP (10(-5)M), abluminal ADP produced vasodilatation, presumably because P2X-purinoceptors were occupied, thereby unmasking P2Y-purinoceptor-mediated dilatation. 6. These results suggest that asymmetric vascular responses of rabbit carotid arteries to adenine nucleotides may be due in part to preferential activation of P2Y-purinergic receptors on endothelium and P2X-purinergic receptors on vascular smooth muscle.

Topics: Acetylcholine; Adenine Nucleotides; Adenosine; Adenosine Triphosphate; Animals; Arginine; Carotid Artery, Common; In Vitro Techniques; Male; Muscle, Smooth, Vascular; Nitroarginine; Nitroprusside; Phenylephrine; Rabbits; Vasoconstriction; Vasodilation

We studied the effects of L-NG-nitro-arginine (L-NOARG), which inhibits nitric oxide (NO) biosynthesis from L-arginine, on the non-adrenergic, non-cholinergic (NANC)-mediated relaxation induced by nicotine in isolated rat duodenum. L-NOARG reduced nicotine-induced relaxation, and L-arginine prevented the inhibitory effect of L-NOARG. However, L-NOARG did not inhibit the tetrodotoxin-insensitive relaxation induced by adenosine 5'-triphosphate, alpha, beta-methyleneadenosine 5'-triphosphate, thyrotropin-releasing hormone or the calcitonin gene-related peptide. Endogenous NO thus could possibly be involved in the NANC-mediated relaxation of rat duodenum induced by nicotine.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Arginine; Calcitonin Gene-Related Peptide; Duodenum; Hexamethonium Compounds; In Vitro Techniques; Male; Muscle Relaxation; Muscle, Smooth; Nicotine; Nitroarginine; Rats; Rats, Inbred Strains; Tetrodotoxin; Thyrotropin-Releasing Hormone