Based upon catecholamine histofluorescence and capacity for neuronal uptake of norepinephrine, extra- and intrapulmonary arteries are well supplied by adrenergic nerves. In isolated segments of arteries larger than 0.6 mm in diameter, these nerves release sufficient transmitter to cause vasoconstriction. However, in arteries smaller than 0.6 mm in diameter, both nerve stimulation and NE application elicited either very small responses or none at all. The vascular smooth muscle was responsive under the experimental conditions, since all arterial segments constricted in response to 5HT, histamine, and KCl, and the maximal effects of the three agents were equal. It is not yet known whether the poor reactivity of small arteries to NE and adrenergic nerve stimulation is peculiar to the rabbit pulmonary vascular bed, and whether segments of the pulmonary vascular tree farther downstream than those studied are more reactive to sympathetic stimulation. Possibly the sympathetic control of vascular tone is restricted to the relatively large arteries. Reduction in the magnitude of the contractile response, rather than sensitivity to NE, appears to account for the diminution of vessel response as the vessel becomes smaller. It is speculated that, in the pulmonary vasculature through which the output of the right heart passes to the left, an extensive arterial constriction accompanying sympathetic discharge resulting in major changes in blood flow is undesirable.

Transmural nerve stimulation (TNS) with 0.3-msec pulses between 1 and 25 Hz dilated cat cerebral artery segments in the presence of active muscle tone. Maximum vasodilatation occurred at 8 Hz. The dilator response to exogenous acetylcholine, but not to TNS, was abolished by atropine. Neither physostigmine nor hemicholinium affected the dilator response to TNS, which persisted after administration of guanethidine, phenoxybenzamine, propranolol, reserpine, and chronic sympathectomy. However, it was abolished by tetrodotoxin and cold storage. When examined histochemically, cat and rabbit cerebral arteries exhibited a rich plexiform distribution of acetylcholinesterase which was not affected appreciably by sympathetic denervation. These results suggest that vasodilation is not mediated through modification of sympathetic activity. They also indicate the existence of a nonadrenergic, possibly noncholinergic, vasodilator innervation in cat cerebral arteries. Preliminary studies suggest that the transmitter is not histamine, ATP, prostaglandins, gamma-aminobutyric acid, dopamine, or serotonin. The cat cerebral artery segments contrast with the isolated rabbit cerebral arteries which predominantly constrict in response to TNS and show a small dilator response.

The effect of ATP and its congeners on the adrenergic neuroeffector transmission was evaluated in isolated blood vessels of the rabbit. ATP, ADP, AMP and adenosine inhibited the contractile response of the portal vein to adrenergic nerve stimulation, with a threshold concentration of the order of 0.1 muM and ED50 of about 1 microM. These agents, but not papaverine, inhibited the nerve stimulation-induced response in preference to the norepinephrine- or serotonin-induced response in the portal and saphenous veins and pulmonary and ear arteries. In the portal vein labeled with [3H]norepinephrine, ATP diminished the nerve stimulation-induced efflux of tritiated material. This nucleotide also reduced the KCl-induced tritium efflux but not the tyramine induced-efflux in the [3H]norepinephrine-labeled thoracic aorta. ATP had no significant effect on the uptake of [3H]norepinephrine in the portal vein, ear artery and thoracic aorta. Indomethacin and theophylline partially blocked the inhibitory action of ATP on the neurogenic constrictor response in some of the ear artery and saphenous vein preparations. Desipramine, atropine, propanolol, haloperidol and 2,2'-pyridylisatogen, a blocking agent against ATP in the taenia coli, were without such antagonistic effect. The results are consistent with a proposed negative feedback modulator role of ATP or a related purine compound in adrenergic transmission.

The uptake of traited norepinephrine in isolated rabbit mesoduodenal blood vessels was measured. Neuronal uptake was estimated utilizing the inhibitory effect of cocaine, and expressed on the basis of wet and dry tissue weights as well as circumferential area of the vascular wall. This area was presumed to approximate the area of the adrenergic nerve terminal plexus. The wet weight of smaller tissues was apt to be underestimated due to excessive drying during weighing; dry weight was more consistent over a wide range of tissue size. Either on the basis of weight or circumferential are, neuronal uptake in arteries increased as the diameter diminished, but uptake was practically constant in all segments of the veins. Arterial uptake per unit circumferential area was greater than in the accompanying veins, but this was not necessarily the case when uptake was expressed per unit weight. Neuronal norepinephrine may be a useful index of adrenergic nerve density. On this basis it is suggested that the adrenergic neural vasoconstriction increases with decrease in diameter of both arteries and veins in rabbit mesoduodenum.

1.1. We recorded isometric contractile force of rabbit pulmonary artery after application of norepinephrine (50 μM), plotted semilogarithmic graphs of force development over time, and calculated rates of force development.2.2. The normal contractile response contained three phases: an initial fast, a short intermediate and a final slow. Correlation coefficients for each phase and differences between rates of force development of each phase were significant (P < 0.05).3.3. Ruthenium red (1 mM) removed only the slow phase and significantly reduced the rates of the fast and intermediate phases.4.4. A calcium-free solution removed both the slow and intermediate phases and significantly reduced the rate of the fast phase.