YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==ALCOHOL AND VASODILATATION== 4 AUTHOR Chaudhuri KR AUTHOR Maule S AUTHOR Thomaides T AUTHOR Pavitt D AUTHOR Mathias CJ TITLE Alcohol ingestion lowers supine blood pressure, causes splanchnic vasodilatation and worsens postural hypotension in primary autonomic failure. SOURCE J Neurol; VOL 241, ISS 3, 1994, P145-52 ABSTRACT Patients with pure autonomic failure (PAF) and multiple system atrophy (MSA) may complain of feeling light-headed after alcohol ingestion particularly on assumption of the upright posture. The reasons for this have not been investigated. We therefore studied the effects of oral alcohol (40% vodka in sugar-free orange juice) and placebo (juice only) on the systemic and regional (including superior mesenteric artery, SMA) blood flow in nine patients with PAF and six patients with MSA. After alcohol, there was a fall in supine blood pressure (BP) and vasodilatation in the SMA but no change in cardiac output, or forearm muscle and cutaneous blood flow in either PAF or MSA; BP fell further during head-up tilt with no changes in levels of plasma catecholamines. After placebo, there were no changes while supine. We conclude that alcohol lowers supine BP and dilates the SMA with no change in muscle or cutaneous blood flow. Alcohol also enhances the fall in BP during head-up tilt. This may explain the symptoms experienced by PAF and MSA patients after alcohol. 15 AUTHOR ALVING K TITLE Airways vasodilatation in the immediate allergic reaction: Involvement of inflammatory mediators and sensory nerves. SOURCE ACTA PHYSIOL SCAND SUPPL; 0 (597). 1991. 1-64. ABSTRACT BIOSIS COPYRIGHT: BIOL ABS. Systemic capsaicin treatment of the pig depletes the content of sensory neuropeptides (CGRP and tachykinins) in the airways mucosa and skin, without affecting sympathetic and parasympathetic nerves containing NPY and VIP, or the presence and appearance of inflammatory cells including mast cells. Acute capsaicin exposure caused release of sensory neuropeptides and catecholamines, and marked vasodilation in the airways and skin, without signs of plasma protein extravasation or bronchoconstriction. Capsaicin pretreatment effectively desensitizes against local challenges with capsaicin in the airways and skin, as revealed by the absence of vasodilatory response 2 days later. Cigarette smoke exposure induces marked vasodilatation, lasting for about 5 min in both the upper and lower airways, which seems not to be primarily caused by particulate matter or nicotine in the smoke. Except for a minor capsaicin-sensitive component in the nasal circulation, these responses probably do not involve neural activation, mast cell degranulation or prostaglandin formation. Rather, it is concluded that vapour phase components act on the vessels via unknown mechanisms. Sensitization of pigs with s.c. injections of ascaris antigen was successful, resulting in typical wheal and flare reactions in the skin and bronchoconstriction after local challenge with antigen. The reactivity to ascaris is probably mediated by antibodies of the IgE isotype. Histamine-containing mast cells and sensory neuropeptide-containing nerve fibres show close morphological association around blood vessels in the pig skin. Both alcian blue-positive mast cells and capsaicin-sensitive sensory nerves are present close to the pig airways epithelium. Sensory neuropeptide-containing nerves are also abundant around airways mucosal blood vessels, whereas the bronchial smooth muscle is sparsely innervated. Allergen and histamine injection in the skin caused similar responses consisting of flare and protein extravasation. Allergen challenge in the airways induces marked vasodilatation lasting for 60-90 min in the pig bronchial and nasal circulations. Histamine seems to be important in the early phase (0-20 min) of these responses in the airways, while cyclo-oxygenase products (possibly PGD2) may be responsible for the long-lasting component. A cyclo-oxygenase product is presumably also released from the lung into the circulation after bronchial allergen challenge and thereby induces a delayed, long-lasting nasal vasodilatation. Histamine may be the main bronchoconstrictor agent released in the immediate allergic reaction of the pig. The flare, but not the protein extravasation reaction, to allergen and histamine injections in the skin, was inhibited by capsaicin pretreatment. Aerosolized histamine and bradykinin, but not PGD2, seem to cause airways vasodilatation partly via activation of capsaicin-sensitive sensory nerves. Nedocromil sodium reduces the airways vasodilatation response bradykinin and the histamine-induced nasal vasodilatation in the same manner as capsaicin pretreatment. It may thus be suggested that nedocromil solution acts at least partly by inhibiting sensory nerve activation by inflammation mediators. Nedocromil solution also reduced the allergen-induced bronchoconstriction, indicating an inhibitory action on mast cells as well. Capsaicin-sensitive sensory nerves are probably mainly involved in the airways vasodilatation seen after allergen challenge. In conclusion, a large animal model has been developed where the influence of irritants and all(ABSTRACT TRUNCATED AT 400 WORDS) 26 AUTHOR Kalant H AUTHOR Le AD TITLE Effects of ethanol on thermoregulation. SOURCE Pharmacol Ther; VOL 23, ISS 3, 1983, P313-64 (REF: 385) ABSTRACT Clinical reports of accidental hypothermia in alcohol intoxicated individuals exposed to low ambient temperature ( Paton , 1983) have generally been borne out by experimental studies in healthy volunteers. Small doses of ethanol, given to human subjects at normal ambient temperature (Ta), have very little effect on body temperature but a combination of large dose, low Ta and vasodilatation provoked by strenuous exercise, causes a sharp fall in rectal temperature. In experimental animals, the use of relatively larger doses of alcohol and more extreme temperatures, both above and below the thermoneutral zone, has shown that the effect of ethanol is essentially poikilothermic, i.e. an impairment of adaptation to both heat and cold. This effect has been studied in greater detail, in relation to each of the basic thermoregulatory processes. Though small doses of alcohol may increase the metabolic rate under some circumstances, the most common effect at low Ta is inhibition of shivering and therefore reduction of thermogenesis. At the same time it tends to cause increased heat loss by cutaneous vasodilatation. This makes for a greater feeling of comfort in the cold exposed subjects but increases in rate of fall of core temperature. The combination of decreased thermogenesis and increased heat loss, despite falling body temperature, is suggestive of a lowering of the set-point of the thermoregulatory control mechanisms. Consistent with this is a slight increase in ventilatory heat loss after low doses of ethanol but larger doses cause respiratory depression, so that heat loss through the lungs is minor. However, at high Ta ethanol caused hyperthermia in experimental animals and shows enhanced lethality, so that impairment of thermoregulatory effector mechanisms seems to be at least as important as change in set-point. Studies of the effects of ethanol on electrophysiological activity of single neurons in the pre-optic area and anterior hypothalamus (POAH), biochemical activities of neuronal membranes, hypothalamic blood flow, conventional neurotransmitters, amino acid putative neurotransmitters, neuropeptides, prostaglandins and inorganic ions have all failed so far to yield a clear comprehensive picture of the mechanisms by which ethanol affects thermoregulation. In each case, contradictory evidence has been obtained concerning the consequences of ethanol administration, whether by oral, intraperitoneal, intravenous, intracerebroventricular, or direct local (POAH) route.(ABSTRACT TRUNCATED AT 400 WORDS)