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

Abstract

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.

Role of ROS signaling in differential hypoxic Ca2+ and contractile responses in pulmonary and systemic vascular smooth muscle cells

“…Studies of oxygen sensing in carotid body cells by the same group, however, have failed to find an effect on Ca V channel gating (Lopez-Barneo et al , 1993). These results, together with previous reports that relaxation of rabbit pulmonary arteries is usually seen during hypoxic stimulation (Marriott & Marshall, 1990;MacLean et al , 1993;Vadula et al , 1993), suggest that such a mechanism may not play an important role in hypoxic increase in [Ca 2+ ] i . As described above, a number of reports have shown that hypoxic contraction in isolated lungs, PAs and PASMCs are relatively insensitive to multiple Ca V channel blockers (Demiryurek et al , 1993;Jabr et al , 1997;Robertson et al , 2000;Shimoda et al , 2000;Sham et al , 2000;Dipp & Evans, 2001;Kang et al , 2002).…”

Influence of endothelial nitric oxide on neurogenic contraction of human pulmonary arteries

“…These findings suggest that nitric oxide from endothelial cells is responsible for the depressant influence of endothelium on the neurogenic-induced contraction, and agree with previous observations in guinea-pig and rabbit pulmonary arteries [7,10]. In some vessels [9] as well as in other tissues [17,18], nitric oxide might be directly released from perivascular nerve fibres as a transmitter to counteract neurogenic contractions.…”

“…The inhibitory effect of endothelium on the contractile response to adrenergic nerve stimulation seems to be due to the release of nitric oxide from endothelial cells [6][7][8]. A direct release of nitric oxide from perivascular nerve endings or from smooth muscle cells has also been considered [9,10].…”

Regional variation in electrically‐evoked contractions of rabbit isolated pulmonary artery

“…19.6 mN tension is the standard tension normally used to preload pulmonary arterial segments in mechanical studies (Nedergaard & Schrold, 1977; MacLean et al ., 1993a, b; Sim & Soh, 1995; Sim & Chai, 1996; Tan & Sim, 2000). Intrapulmonary artery rings are much smaller than extrapulmonary segments, therefore the resting tension was varied to determine if this factor could in some way contribute to the generation of the slow contraction.…”

“…It is well known that sympathetic nerve stimulation elicits noradrenaline release, which by action at α 1 ‐adrenoceptors, produced a prazosin‐sensitive contraction of the extrapulmonary artery (Nedergaard & Abrahamsen, 1988; MacLean et al ., 1993a). However, in the present study, the slow contraction of the intrapulmonary artery was largely unaffected by α‐adrenoceptor antagonists.…”