Autonomic control of cardiorespiratory interactions in fish, amphibians and reptiles

Control of the heart rate and cardiorespiratory interactions (CRI) is predominantly parasympathetic in all jawed vertebrates, with the sympathetic nervous system having some influence in tetrapods. Respiratory sinus arrhythmia (RSA) has been described as a solely mammalian phenomenon but respiration-related beat-to-beat control of the heart has been described in fish and reptiles. Though they are both important, the relative roles of feed-forward central control and peripheral reflexes in generating CRI vary between groups of fishes and probably between other vertebrates. CRI may relate to two locations for the vagal preganglionic neurons (VPN) and in particular cardiac VPN in the brainstem. This has been described in representatives from all vertebrate groups, though the proportion in each location is variable. Air-breathing fishes, amphibians and reptiles breathe discontinuously and the onset of a bout of breathing is characteristically accompanied by an immediate increase in heart rate plus, in the latter two groups, a left-right shunting of blood through the pulmonary circuit. Both the increase in heart rate and opening of a sphincter on the pulmonary artery are due to withdrawal of vagal tone. An increase in heart rate following a meal in snakes is related to withdrawal of vagal tone plus a non-adrenergic-non-cholinergic effect that may be due to humoral factors released by the gut. Histamine is one candidate for this role.

Action mechanisms of NANC neurotransmitters in smooth muscle of guinea pig ileum

The relaxation induced by stimulation of the inhibitory non-adrenergic, non-cholinergic (iNANC) nerve is mediated by the release of iNANC neurotransmitters such as nitric oxide (NO), vasoactive intestinal peptide (VIP) and adenosine triphosphate (ATP). The mechanisms of NO, VIP or ATP-induced relaxation have been partly determined in previous studies, but the detailed mechanism remains unknown. We tried to identify the nature of iNANC neurotransmitters in the smooth muscle of guinea pig ileum and to determine the mechanism of the inhibitory effect of nitric oxide. We measured the effect of NO-donors, VIP and ATP on the intracellular Ca2+ concentration((Ca2+)i), by means of a fluorescence dye (fura 2) and tension simultaneously in the isolated guinea pig ileal smooth muscle. Following are the results obtained. 1. Sodium nitropnisside (SNP: 10(-5) M) or S-nitro-N-acetyl-penicillamine (SNAP: 10(-5) M) decreased resting (Ca2+)i and tension of muscle. SNP or SNAP also inhibited rhythmic oscillation of (Ca2+)i and tension. In 40mM K+ solution or carbachol (CCh:10(-6) M)-induced precontracted muscle, SNP decreased muscle tension. VIP did not change (Ca2+)i and tension in the resting or precontracted muscle, but ATP increased resting (Ca2+)i and tension in the resting muscle. 2. 1H-(1,2,4)oxadiazol(4,3-a)quinoxalin-1-one (ODQ:1 muM), a specific inhibitor of soluble guanylate cyclase, limited the inhibitory effect of SNP. 3. Glibenclamide (10 muM), a blocker of KATP channel, and 4-aminopyridine (4-AP:5 mM), a blocker of delayed rectifier K channel, apamin (0.1 muM), a blocker of small conductance KCa. channel had no effect on the inhibitory effect of SNP. Iberiotoxin (0.1 muM), a blocker of large conductance KCa channel, significantly increased the resting (Ca2+)i, and tension, and limited the inhibitory effect of SNP. 4. Nifedipine (1 muM) or elimination of external Ca2+ decreased not only resting (Ca2+)i and tension but also oscillation of (Ca2+)i and tension. Ryanodine (5 muM) and cyclopiazonic acid (10 muM) decreased oscillation of (Ca2+)i and tension. 5. SNP decreased Ca2+ sensitivity of contractile protein. In conclusion, these results suggest that 1) NO is an inhibitory neurotransmitter in the guinea pig ileum, 2) the inhibitory effect of SNP on the (Ca2+)i and tension of the muscle is due to a decrease in (Ca2+)i by activation of the large conductance KCa channel and a decrease in the sensitivity of contractile elements to Ca2+ through activation of G-kinase.

The Role of Nitric Oxide in the Relaxation of Canine Corpus Cavernosum Smooth Muscle / 대한비뇨기과학회지

Nitric Oxide(NO) has been known to be endothelium-derived relaxing factor in blood vessels, and to be nonadrenergic-noncholinergic(NANC) neurotransmitter involved in the relaxation of corpus cavernosum smooth muscle of man and rabbit. This study was initiated to determine NANC inhibitory neurotransmission in the canine corpus cavernosum. Using organ bath, isometric tension measurements were made in strips of canine corpus cavernosum. Transmural electrical stimulation of corporal tissue strips, in the presence of adrenergic blockade with bretylium and muscarinic receptor blockade with atropine, caused frequency-dependent relaxation. This relaxation was inhibited significantly by nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester(L-NAME). Our findings suggest that there should be nonadrenergic-noncholinergic neurotransmitter in the canine corpus cavernosum smooth muscle and it could be nitric oxide. Canine erectile tissue might serve as in vitro model for further investigation of corpus cavernosal smooth muscle pathophysiology.