Endogenous nitric oxide modulates adrenergic neural vasoconstriction in guinea‐pig pulmonary artery

Self Cite

1 Nonadrenergic, noncholinergic (NANC) nerves mediate vasodilatation in guinea-pig pulmonary artery (PA) by both endothelium-dependent and endothelium-independent mechanisms. The transmitter(s) involved in the endothelium-independent pathway have not yet been identified. We have therefore investigated the possibility that nitric oxide (NO) and guanosine 3',5'-cyclic monophosphate (cyclic GMP) may mediate this neural vasodilator response in guinea-pig branch PA rings denuded of endothelium. 2 Electric field stimulation (EFS, 50 V, 0.2 ms) induced a frequency-dependent (1-24 Hz), tetrodotoxin-sensitive relaxation of the U44069-precontracted PA rings in the presence of adrenergic and cholinergic blockade. 3 The NO synthase inhibitors NG-monomethyl L-arginine (L-NMMA, 100 pM) and NG-nitro L-arginine methyl ester (L-NAME, 30 pM), and the guanylyl cyclase inhibitor methylene blue (5 pM) inhibited the EFS (16 Hz)-induced relaxation by 53 ± 5, 74 + 9 and 82 ± 9% respectively (n = 5-7, P<0.01, compared with control rings).4 Excess concentrations of L-, but not D-arginine (300 gM) completely reversed the inhibitory effect of L-NMMA. 5 The EFS-elicited relaxation (4 Hz) was potentiated by 1 gM zaprinast, a type V phosphodiesterase inhibitor which inhibits guanosine 3':5'-cyclic monophosphate (cyclic GMP) degradation, but was unaffected by 0.1 gM zardaverine, a type III/IV phosphodiesterase inhibitor which inhibits cyclic AMP degradation. 6 EFS (50 V, 0.2 ms, 16 Hz) induced a 3 fold increase in tissue cyclic GMP content, an action which was inhibited by L-NMMA (100;LM).7 Pyrogallol (100IM), a superoxide anion generator, also inhibited the EFS-induced relaxation by 53 ± 9%, and this effect was prevented by superoxide dismutase. 8 Chemical sympathetic denervation with 6-hydroxydopamine had no effect on the relaxant response to EFS in the endothelium-denuded PA rings.9 In endothelium-denuded branch PA rings at resting tone, L-NMMA (100 JM) significantly augmented the adrenergic contractile response, an effect which was completely reversed by L-arginine, but not by D-arginine. In the same groups of vessel rings, L-NMMA had no significant effect on the matched contractile response to exogenous noradrenaline. 10 These results suggest that NO may be released from intramural nerve endings other than adrenergic nerves (probably NANC nerves), and this leads to vasodilatation via activation of guanylyl cyclase.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of nitric oxide and guanosine 3′,5′‐cyclic monophosphate in mediating nonadrenergic, noncholinergic relaxation in guinea‐pig pulmonary arteries

Liu

Crawley

Rohde

et al. 1992

Self Cite

“…However, it is possible that NO could be released from nerves, endothelial cells lining blood vessels or other cell types that express NO synthase (Moncada et al, 1991). NO causes relaxation of airway smooth muscle (Tucker et al, 1990;Li & Rand, 1991) and pulmonary artery (Liu et al, 1991). The receptor for NO in several tissues and cells including nerves appears to be soluble guanylate cyclase (Rapoport & Murad, 1983;Moncada, 1992).…”

Section: Discussionmentioning

confidence: 99%

The role of nitric oxide in cholinergic neurotransmission in rat trachea

Sekizawa

Fukushima

Ikarashi

et al. 1993

1 We have investigated the role of nitric oxide (NO) in cholinergic contraction in rat trachea.2 Methylene blue (1O nM to 30 fLM) potentiated cholinergic contraction induced by electrical field stimulation (EFS) at 5 Hz in a concentration-dependent fashion. At a concentration of 30 i1M, methylene blue decreased responses to log EFS frequency, producing 50% of maximum contraction from a control value of 0.74 ± 0.09 Hz to 0.30 ± 0.05 Hz without a significant effect on concentration-response curves to acetylcholine (ACh).3 NG-monomethyl-L-arginine (L-NMMA; 100 1AM) also potentiated cholinergic contraction induced by EFS at 5 Hz (131.5 ± 4.6% of control) without having any effect against ACh (3 jiM)-induced contractions. Likewise, L-NMMA (10011M) significantly increased EFS (5 Hz)-evoked release of ACh from tracheal segments into the bath solution (51.4 ± 4.0 pmol ml-' in the presence of L-NMMA and 35.0 ± 1.8 pmol ml-' in the absence of L-NMMA, respectively).4 Administration of NO (present in acidified soluton of NaNO2) (1 nM to 10 tM) and sodium nitroprusside (100 nM to 10 ytM) concentration-dependently reduced EFS (5 Hz)-induced cholinergic contractions without having a significant effect on ACh (3 tLM)-induced contractions. These results were unaffected by prior exposure of the tissues to L-NMMA (100 ftM). 7 These results suggest that an endogenous NO-like factor may mediate prejunctional inhibition of cholinergic contraction through a cyclic GMP-dependent mechanism in rat trachea.

“…The vascular endothelium has an inhibitory effect on adrenergic nerve stimulation in the rabbit carotid artery (Tesfamariam et al, 1987) and rat caudal artery (Hynes et al, 1988) and it is believed that endotheliumreleased vasorelaxant factors are responsible (Tesfamariam et al, 1987). Recently, Liu et al (1991) implicated nitric oxide as a modulator of neurogenic responses in guinea-pig pulmonary arteries. We have shown that transient inhibition of nitric oxide is responsible for the transient vasoconstrictor response to acute hypoxia in rabbit pulmonary arteries (MacLean & McGrath, 1991).…”

Section: Introductionmentioning

confidence: 99%

Influences of the endothelium and hypoxia on neurogenic transmission in the isolated pulmonary artery of the rabbit

MacLean

McCulloch

Macmillan

et al. 1993

1The effects of nitric oxide (10-6 M), NW-nitro-L-arginine methylester (L-NAME, 10-M, an inhibitor of nitric oxide synthase), endothelium removal, hypoxia and selective ax-adrenoceptor antagonists on responses to nerve electrical field-stimulation (EFS) were studied in the rabbit isolated pulmonary artery.2 EFS induced frequency-dependent contractions which were abolished by prazosin (xi-adrenoceptor antagonist) and unaffected by rauwolscine (M2-adrenoceptor antagonist). EFS-induced responses were potentiated by L-NAME and inhibited by nitric oxide. The effect of L-NAME was reversed by the presence of L-arginine (2 x 10-4 M), which had no effect on its own. In the presence of L-NAME, the EFS-induced responses were reduced by rauwolscine and the residual responses were abolished by prazosin. 3 Removal of the vascular endothelium increased the maximum contractile response to EFS but did not inhibit the ability of L-NAME to potentiate contractile responses to EFS. 4 Hypoxia inhibited the contractile response to EFS. This effect of hypoxia was also seen in the presence of L-NAME and in endothelium rubbed preparations. 5 In conclusion, the endothelium modulates EFS-induced contractions in the rabbit pulmonary artery. The contraction induced by EFS was inhibited by nitric oxide, but potentiated by the nitric oxidesynthase inhibitor, L-NAME. The effect of L-NAME was not mediated solely through the endothelium and revealed involvement of a2-adrenoceptors in EFS-induced contraction. Hypoxia inhibited neurogenic responses in rabbit isolated pulmonary arteries.