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

• Published in: British journal of pharmacology Vol. 137; no. 4; pp. 488 - 496
• Main Authors: Jackson, V Margaret, Trout, Stephen J, Cunnane, Tom C
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2002
• Subjects: Angiotensins - pharmacology; Animals; biphasic; bretylium; contraction; Electric Stimulation - methods; field stimulation; In Vitro Techniques; Male; monophasic; NANC; Pulmonary Artery - drug effects; Pulmonary Artery - physiology; Rabbit pulmonary artery; Rabbits; smooth muscle; sympathetic nerves; Vasoconstriction - drug effects; Vasoconstriction - physiology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704863

Electrically‐evoked contractions in different regions of the rabbit isolated pulmonary artery have been investigated using stimulation parameters generally assumed to stimulate nerves selectively. In extrapulmonary artery, trains of stimuli (10 Hz; pulse width 0.1 ms) evoked monophasic contractions. In contrast, a biphasic contraction was evoked in the intrapulmonary artery consisting of an initial fast component followed by a secondary very long‐lasting component. The contraction in the extrapulmonary artery was prazosin‐sensitive (1 μM) whereas that in the intrapulmonary artery was prazosin‐resistant. α,β‐Methylene ATP (1 μM), atropine (1 μM), losartan (1 μM), BIBO3304 (1 nM) or nifedipine (1 μM) had no effect on the biphasic contraction of the intrapulmonary artery. Bretylium (2 μM) abolished the contraction of extrapulmonary artery but only partially inhibited the initial component in the intra region with no effect on the second component. Tetrodotoxin (0.3–1 μM), abolished the contraction of extrapulmonary artery but only partially reduced the electrically‐evoked contraction of intrapulmonary artery. Removal of the endothelium and application of sulphisoxazole (0.6–22 μM) had no effect. Varying the resting tone on the arteries, or applying gadolinium, had no effect on contractions. Using confocal microscopy and calcium imaging, reproducible whole cell calcium transients were evoked in individual smooth muscle cells in intact preparations but only when direct muscle stimulation was used (pulse width of 5–10 ms). No detectable changes in calcium were elicited when brief pulse widths were used (0.1–2 ms). Together, these data suggest that noradrenaline is the neurotransmitter inducing contraction in extrapulmonary artery. Noradrenaline and sympathetic nerves appear to play a less important role in the intrapulmonary artery. The tetrodoxin‐resistant component is not mediated by ATP, NPY, acetylcholine, angiotensins, ET‐1, stretch‐activation or Ca2+ influx through L‐type Ca2+ channels. Smooth muscle cells do not appear to be damaged by the stimulation protocol. The mechanism underlying the long lasting contraction of intrapulmonary artery evoked by brief electrical stimuli remains to be elucidated. British Journal of Pharmacology (2002) 137, 488–496. doi:10.1038/sj.bjp.0704863