Despite its very potent vasodilating action in vivo, acetylcholine (ACh) does not always produce relaxation of isolated preparations of blood vessels in vitro. For example, in the helical strip of the rabbit descending thoracic aorta, the only reported response to ACh has been graded contractions, occurring at concentrations above 0.1 muM and mediated by muscarinic receptors. Recently, we observed that in a ring preparation from the rabbit thoracic aorta, ACh produced marked relaxation at concentrations lower than those required to produce contraction (confirming an earlier report by Jelliffe). In investigating this apparent discrepancy, we discovered that the loss of relaxation of ACh in the case of the strip was the result of unintentional rubbing of its intimal surface against foreign surfaces during its preparation. If care was taken to avoid rubbing of the intimal surface during preparation, the tissue, whether ring, transverse strip or helical strip, always exhibited relaxation to ACh, and the possibility was considered that rubbing of the intimal surface had removed endothelial cells. We demonstrate here that relaxation of isolated preparations of rabbit thoracic aorta and other blood vessels by ACh requires the presence of endothelial cells, and that ACh, acting on muscarinic receptors of these cells, stimulates release of a substance(s) that causes relaxation of the vascular smooth muscle. We propose that this may be one of the principal mechanisms for ACh-induced vasodilation in vivo. Preliminary reports on some aspects of the work have been reported elsewhere.

The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine

Regulation of noradrenaline release by presynaptic receptor systems.

The classification of drugs and drug receptors in isolated tissues.

Presynaptic modulation of neurochemical transmission.

Background and Methods. The use of cocaine, especially one of its alkaloidal forms ("crack"), has been increasingly associated with cerebrovascular disease. To clarify the clinical, radiologic, and pathological features of the events associated with cocaine use, we identified 28 patients at four medical centers who had stroke temporally related to the use of alkaloidal cocaine (during or within 72 hours of use). Results. The 28 patients had the following types of cerebrovascular event: cerebral infarction (n = 18[2hemorrhagic; 1 fatal]) in the areas supplied by the middle cerebral artery (n = 10), anterior cerebral artery (n = 3), posterior cerebral artery (n = 1 ), and vertebrobasilar arteries (n = 4); subarachnoid hemorrhage (n = 5); intraparenchymal hemorrhage (n = 4); and primary intraventricular hemorrhage (n = 1). Eighteen patients (64 percent) had acute neurologic symptoms immediately or within one hour of using cocaine. Fifteen patients (45 percent) with either occlusive or hemorrhagic st...

https://www.nejm.org/doi/pdf/10.1056/NEJM199009133231102

Cerebrovascular complications of the use of the "crack" form of alkaloidal cocaine.

The interaction of serotonin and noradrenaline on the perfused artery

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1967.tb01979.x

The influence of sympathetic innervation on vascular sensitivity to noradrenaline

THE histochemical investigation of tissue sections containing arteries using the fluorescence technique indicates that the noradrenergic structures are superimposed on the outer surface of the smooth muscle layer1. Applying the same technique to the central artery of the rabbit ear, we have found that catecholamine-like fluorescence occurs only in the layer immediately outside the circular smooth muscle, between this muscle and the adventitia. The fluorescence appears as a series of discrete bead-like structures uniformly distributed around the perimeter of the smooth muscle layer as shown in Fig. 1. The histological observations drew our attention to the possibility that uptake of noradrenaline by the artery was restricted to sites at the outer perimeter of the smooth muscle layer and, if so, the action of drugs such as cocaine which inhibit uptake of noradrenaline and sensitize the arterial wall to its action may be influenced by the particular surface of the artery to which the noradrenaline is applied. The following experiment shows that this is the case.

Site of action of cocaine on the perfused artery.

Effect of acetylcholine on the response of the isolated rabbit ear artery to stimulation of the perivascular sympathetic nerves.

the contralateral iris was placed in Krebs bicarintensity of color obtained after #{248}ris appreciably weaker than the original Schiff-aldehyde product, thus stuggesting the quinone moiety as the site of attack. The NOr derivative was found to behave as an acid-base indicator, i.e., has bluish shades at acid pH (e.g., dilute acetic acid) amid reddish shades at alkaline pH (Tris). This in turn suggests some kind of chemical equilibrium in the altered molecule since this behavior is not shown by the original Schiff-aldehyde product. It must be noted that the exact nature of the prodtmcts formed between Schiff’s reagent and aldehydes is unknowmi (cf Stoward. J. Histochem. Cytochenu. 14: 681. 1966). That a positive azo coupling reaction occurs in the presemice of a-naphthol (Tris) is indicated by the great increase in intensity and differemit color shades when this phenol is present than when it is omitted from the Tris buffer. The azo dye formed also behaves as a pH imidicator, i.e., changes from an orange-red to a deep brown-violet color in acid media. Both colors are clearly distinguished from the purplish red of theSchiff-reaction. Intensification of color at acid pH can probably be explained by transformation into the qtiinone tautomer. For Feulgen preparations azo cotupling with anaphthol is best visualized at about p11 12 using a saturated solution of sodium carbomiate in 50% ethanol (instead of Tris) since definite color change to orange-red occurs at higher pIT values. It is also interesting that deoxyribonumcleic acid in Feulgen preparations stained deep blue imistead of the brown-violet color of bemizaldehyde-Schiff derivative and PAS-stained cellulose or mucin. The behavior of the deoxyribose sugar itself has not been investigated.

J. G. Waterson

Papers

The interaction of serotonin and noradrenaline on the perfused artery

The influence of sympathetic innervation on vascular sensitivity to noradrenaline

Site of action of cocaine on the perfused artery.

Effect of acetylcholine on the response of the isolated rabbit ear artery to stimulation of the perivascular sympathetic nerves.

Modification of autofluorescence in the formaldehyde-treated rabbit ear artery by evans blue