nitroarginine and talipexole

To investigate the nitric oxide (NO)-mediated nerve relaxation and its possible modulation by pre-junctional alpha2-adrenoceptors in the pig urinary bladder neck.. Urothelium-denuded bladder neck strips were dissected, and mounted in isolated organ baths containing a physiological saline solution (PSS) at 37 degrees C and continuously gassed with 5% CO2 and 95% O2, for isometric force recording. The relaxations to transmural nerve stimulation (electrical field stimulation [EFS]) or exogenously applied NO were carried out on strips pre-contracted with 1 microM phenylephrine (PhE) and treated with guanethidine (10 microM) and atropine (0.1 microM), to block noradrenergic neurotransmission and muscarinic receptors, respectively.. EFS (0.2-1 Hz, 1 msec duration, 20 sec trains, current output adjusted to 75 mA) evoked frequency-dependent relaxations which were abolished by the neuronal voltage-activated Na+ channel blocker tetrodotoxin (TTX, 1 microM). These responses were potently reduced by the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NOARG, 30 microM) and further reversed by the NO synthesis substrate L-arginine (L-ARG, 3 mM). The alpha2-adrenoceptor agonist BHT-920 (2 microM) reduced the electrically evoked relaxations, its effectiveness being higher on the responses induced by low frequency stimulation. BHT-920-elicited reductions were fully reversed by the alpha2-adrenoceptor antagonist rauwolscine (RAW, 1 microM). Exogenous NO (1 microM-1 mM) induced concentration-dependent relaxations which were not modified by BHT-920, thus eliminating a possible post-junctional modulation.. These results indicate that NO is involved in the non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission in the pig urinary bladder neck, the release of NO from intramural nerves being modulated by pre-junctional alpha2-adrenoceptor stimulation.

Topics: Adrenergic alpha-Agonists; Animals; Arginine; Autonomic Nervous System; Azepines; Electric Stimulation; Enzyme Inhibitors; Female; Isometric Contraction; Male; Muscle Relaxation; Nitric Oxide; Nitric Oxide Synthase Type I; Nitroarginine; Receptors, Adrenergic, alpha-2; Swine; Synaptic Transmission; Tetrodotoxin; Urinary Bladder; Yohimbine

To analyze the effect of hyperthermia on the vascular response, the isometric response of isolated rabbit femoral artery segments was recorded at 37 degreesC and hyperthermia (41 and 44 degreesC). Contraction to potassium (5 x 10(-3)-5 x 10(-2) M) was significantly greater at 41 and 44 than at 37 degreesC and increased by inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine (L-NNA; 10(-4) M) or endothelium removal at 37 degreesC but not at 41 or 44 degreesC. Norepinephrine (10(-9)-10(-4) M) produced a concentration-dependent contraction greater at 41 or 44 than at 37 degreesC and not modified by endothelium removal or L-NNA at either temperature. Phenylephrine (10(-9)-10(-4) M) produced a contraction increased by warming to 44 degreesC but not to 41 degreesC. The specific alpha2-adrenoceptor agonist BHT-920 produced a weak contraction, reduced by the alpha1-adrenoceptor antagonist prazosin (10(-6) M) and increased at 44 degreesC but not at 41 degreesC. The concentration-dependent contraction to endothelin-1 (ET-1; 10(-11)-10(-7) M) was increased by warming to 41 and 44 degreesC and by endothelium removal or L-NNA at 37 degreesC but not at 41 or 44 degreesC. Response to ET-1 was reduced by endothelin ETA-receptor antagonist BQ-123 (10(-5) M) and ETB-receptor antagonist BQ-788 (10(-5) M). In arteries precontracted with ET-1 (10(-8)-3 x 10(-8) M), relaxation to sodium nitroprusside (10(-8)-10(-4) M) was increased at 41 and 44 degreesC vs. at 37 degreesC, but that of ACh (10(-8)-10(-4) M) or adenosine (10(-8)-10(-4) M) was not different at all temperatures studied. Relaxation to ACh, but not adenosine, was reduced similarly by L-NNA at all temperatures studied. These results suggest hyperthermia in muscular arteries may inhibit production of, and increase dilatation to, NO, resulting in unchanged relaxation to ACh and increased constriction to KCl and ET-1, and may increase constriction to stimulation of alpha1-adrenoceptors by NO-independent mechanisms.

Topics: Acetylcholine; Adenosine; Animals; Azepines; Endothelin Receptor Antagonists; Endothelin-1; Femoral Artery; Fever; In Vitro Techniques; Nitric Oxide; Nitroarginine; Nitroprusside; Norepinephrine; Potassium Chloride; Rabbits; Receptors, Adrenergic, alpha; Vasoconstriction; Vasodilation

To study the influence of alpha-adrenergic stimuli on non-adrenergic non-cholinergic (NANC) neurogenic relaxation in isolated horse penile resistance arteries.. Deep intracavernous penile arteries with an internal lumen diameter of 200-500 microns., isolated from the corpus cavernosum of young horses, were mounted in microvascular myographs for isometric tension recording and electrical field stimulation (EFS) of autonomic nerve terminals.. In the presence of guanethidine (10(-5) M) and atropine (10(-7) M) tone of the arteries was raised by the thromboxane analogue, U46619. EFS (1, 4 and 32 Hz) induced frequency-dependent relaxations, which were abolished in the presence of tetrodotoxin, while NG-nitro-L-arginine (L-NOARG, 10(-4) M) abolished the relaxations to EFS at 1 Hz, and significantly reduced the relaxations at 4 Hz and 32 Hz by 82.5 +/- 10.2% and 52.9 +/- 4.7%, respectively (n = 6). EFS induced relaxations of a similar magnitude in penile arteries contracted with U46619 or the alpha 1-adrenoceptor agonist, phenylephrine, while the alpha 2-adrenoceptor agonist, BHT920 (10(-6) M), produced an inhibitory effect on the EFS-evoked relaxations which was inversely related to the stimulus frequency (1, 4 and 32 Hz). BHT920 had no effect on the relaxations induced by exogenous nitric oxide (NO), added as acidified sodium nitrite (10(-6)-10(-3) M). The inhibitory effect of BHT920 on NANC relaxations was reversed by 10(-7) M rauwolscine.. These results suggest that the release of a NANC neurotransmitter primarily thought to be NO is inhibited by stimulation of prejunctional alpha 2-adrenoceptors in horse penile resistance arteries.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adrenergic alpha-Agonists; Animals; Arteries; Azepines; Electric Stimulation; Enzyme Inhibitors; Horses; Male; Muscle Relaxation; Muscle, Smooth, Vascular; Nitric Oxide; Nitroarginine; Penis; Prostaglandin Endoperoxides, Synthetic; Receptors, Adrenergic, alpha-2; Thromboxane A2; Vasoconstrictor Agents