Anthony Carella

Ethanol produces coronary vasospasm: evidence for a direct action of ethanol on vascular muscle

The effects of ethanol and acetaldehyde on basal tension of canine small and large coronary arteries were examined in vitro. Ethanol in a concentration as little as 8.5 mm can induce threshold contractions of coronary arteries. High concentrations of ethanol produce concentration‐dependent coronary vasospasms equivalent to those induced by supra‐maximal concentrations of KCl. Acetaldehyde (10−5 to 10−2m) resulted in concentration‐dependent relaxation of basal tone. Use of a variety of pharmacological antagonists (i.e., phentolamine, methysergide, diphenhydramine, metiamide, propranolol and indomethacin) did not attenuate or prevent the spasmogenic actions of ethanol. These findings could help to explain why alcohol can induce cardiac depression, arrhythmias, cardiomyopathy and the higher than normal incidence of sudden death observed in ‘binge’ drinkers.

Acetaldehyde on vascular smooth muscle: Possible role in vasodilator action of ethanol

Previous studies on intact and isolated blood vessels indicate that ethanol can exert depressant actions on vascular smooth muscle. This study, using isolated rat aortic strips and portal veins, was designed to ascertain whether acetaldehyde (ACT), a major metabolite of ethanol, could exert similar effects. The results indicate that ACT can: (a) inhibit spontaneous mechanical activity and lower baseline tension in aortic strips; (b) depending upon concentration, enhance (abolished by phentolamine) or inhibit such spontaneous contractions in portal veins; (c) dose-dependently attenuate contractions induced by epinephrine, vasopressin, serotonin and KCl; (d) cause non-competitive displacement of the contraction--effect curves of these vasoactive compounds; (e) relax drug-induced contractions of aortic and venous smooth muscle, (f) attenuate Ca2+-induced contractions of K+-depolarized aortas and portal veins. These profound depressant actions of ACT are not attenuated, prevented or mimicked by alpha-adrenergic histaminergic, cholinergic, or serotonergic blocking drugs, nor are they attributable to actions on beta-adrenoreceptors, or release of prostaglandin-like substance. The direct vasodepressant actions of ACT on vascular smooth muscles may play significant roles in alcohol-induced peripheral vasodilatation and hypotension, and cardiovascular collapse noted in the alcohol-Antabuse reaction.

EFFECTS OF KETAMINE ON VASCULAR SMOOTH MUSCLE FUNCTION

1 In vitro studies were undertaken on rat aortic strips and portal vein segments to determine whether or not the amine‐type anaesthetic, ketamine, can exert direct actions on vascular smooth muscle. 2 Ketamine was found to inhibit development of spontaneous mechanical activity and lower basal tension. This action took place with ketamine concentrations found in anaesthetic plasma concentrations, i.e., 1 × 10−5 to 2 × 10−4 m. 3 Ketamine (10−5 to 10−3 m) dose‐dependently attenuated contractions induced by adrenaline, noradrenaline, angiotensin II, vasopressin and KCl. These inhibitory actions were Observed with ketamine added either before or after the induced contractions. 4 Ca2+‐induced contractions of K+‐depolarized aortae and portal veins were also attenuated, dose‐dependently, by ketamine. 5 In contrast to the above inhibitory actions, ketamine (2 × 10−6 to 1 × 10−4 m) was found to potentiate specifically 5‐hydroxytryptamine(5‐HT)‐induced contractions of both aortic and venous smooth muscle. However, this was only observed if ketamine was added after 5‐HT had initiated a contractile response. 6 All of the inhibitory, as well as 5‐HT‐potentiating, effects were completely, and almost immediately, reversed upon washing out the anaesthetic from the organ baths. 7 A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects induced by ketamine. 8 These data suggest that rat plasma concentrations of ketamine commonly associated with induction of surgical anaesthesia can induce, directly, relaxation and contractile potentiation of vascular muscle. 9 These diverse findings may aid in explaining the well‐known biphasic pressor actions of ketamine.

Adverse effects of artificial buffers on contractile responses of arterial and venous smooth muscle.

1 In vitro studies were undertaken on rat aortic strips and portal vein segments in order to determine whether or not several commonly used artificial buffers, i.e., tris(hydroxymethyl) aminomethane (Tris), N‐2‐hydroxyethylpiperazine‐N′‐2‐ethanesulphonic acid (HEPES), morpholine propanesulphonic acid (MOPS), N, N bis(2‐hydroxyethyl) glycine (BICINE) and 1,4‐piperazinediethanesulphonic acid (PIPES), can exert direct actions on vascular smooth muscle. 2 All artificial buffers used in 5 mm concentrations were found to inhibit development of spontaneous mechanical activity. 3 Tris, HEPES, MOPS, BICINE and PIPES markedly attenuated contractions induced by adrenaline, angiotensin and KCl. The fast phase components of the agonist‐induced contractions were either obliterated or reduced in the presence of the artificial buffers. The sustained slow phase components were greatly reduced and retarded by the artificial buffers. 4 The relative order of artificial buffer potency (i.e., from 100% to 14% inhibition) seems to depend upon the agonist and type of smooth muscle. 5 All of these inhibitory effects were reversible, since normal contractile responses and spontaneous mechanical activity could be obtained by simply reincubating the smooth muscles in Krebs‐Ringer bicarbonate buffer. 6 A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects of Tris, HEPES, MOPS, PIPES and BICINE. 7 These data show that five of the most commonly used artificial buffers, to study muscles in vitro, exert adverse effects on contractility of arterial and venous smooth muscle.

Adverse effects of tris, hepes and mops buffers on contractile responses of arterial and venous smooth muscle induced by prostaglandins

The influence of artificial buffers, Tris, HEPES and MOPS, on PGA1, B2 and F2 alpha-induced contractile responses of isolated rat aorta and portal vein was investigated. All three buffers, in 5mM concentration, when substituted for bicarbonate and phosphate anions, differentially attenuated PG-induced contractile responses; the vein responses exhibited the greater sensitivity to artificial buffer inhibition. In the presence of the artificial buffers, the PG-induced fast phase contractile components on the arterial smooth muscle were obliterated and the slow, tonic components were markedly depressed. PG contractile concentration-effect curves were shifted, differentially, to the right, concomitant with differential reductions in maximum tensions. Reincubation of the vascular tissues in normal Krebs-Ringer bicarbonate for 30-60 min resulted in a complete restoration of full PG-induced contractions. These results support the idea that Tris, HEPES and MOPS may interfere with the binding, translocation and utilization of calcium ions in vascular smooth muscle cells. One must be cautious regarding conclusions drawn for calcium-dependent responses obtained in smooth muscles in which Tris, HEPES or MOPS was the sole buffering agent.

HDFx: A Recently Discovered Biologic and its Potential Use in Prevention andTreatment of Hemorrhagic Fever Viruses and Antibiotic-Resistant Superbugs

Recently, we have reported on the discovery of a new, conserved protein (35-40 kDa) that protects rats, mice, guinea-pigs, and rabbits against lethal hemorrhage, endotoxins, live lethal bacterial and fungal microorganisms, and traumatic injuries when given prophylactally and therapeutically. HDFx was found to stimulate several arms of the innate immune system (e.g. macrophages, NK cells). HDFx was also found to stabilize the microcirculation, prevent rupture and leakage of postcapillary venules, prevent adhesion of platelets to endothelium and loss of platelets, stabilize falls in arterial blood pressure, and prevent stasis and pooling of blood in the postcapillary vessels, as observed by intra-vital high-resolution TV microscopy. HDFx also stimulates phagocytic uptake of foreign particulate matter and bacteria by liver Kupffer cells, splenic macrophages, and circulating macrophages. It also prevents explosive release of cytokines and chemokines from macrophages and lymphocytes in animals subjected to live bacteria, endotoxins, trauma and combined injuries. Surprisingly, HDFx was found to accelerate wound healing and aid the regeneration of tissues. Repeated administration of HDFx, over many months, does not result in either diminished protective activity or detectable organ or tissue pathologies. One of the major consequences of infections and wars/conflicts is loss of the ability to regenerate normal physiologic functions of numerous organs and tissues. A major characteristic of invasion of the body by septic-endotoxic microorganisms and hemorrhagic fever viruses (HFVs) is that these entities eventuate in rupture of the microvessels in the capillary circulation of numerous organs and tissues leading to massive blood and fluid loss, making the body susceptible to superimposed infections and loss of immuno-competence. About 100 million people are infected worldwide, annually, with about 60,000 to 75,000 deaths per year from HFVs. Added to these numbers are the numerous hospital-borne and food-borne infections along with infections resulting from major disasters (hurricanes, tornados, earthquakes, etc.) that cause 75,000 to 100,000 deaths per year in the U.S.A. alone. The ability and uniqueness of HDFx to minimize infections, accelerate wound healing, and promote tissue regeneration should greatly aid treatment and recovery of these victims and be of great value in infections from HFVs and on battlefields.

Exposure to High Levels of Noise Poses Hazards and Risks for Development of Hypertension and Heart Disease: Potential Roles of Unrecognized Ionized Hypomagnesemia and Release of Ceramides and Platelet-Activating Factor

Recommended Citation Altura, B. M., Gebrewold, A., Carella, A., Shah, N. C., & Altura, B. T. (2018). Exposure to High Levels of Noise Poses Hazards and Risks for Development of Hypertension and Heart Disease: Potential Roles of Unrecognized Ionized Hypomagnesemia and Release of Ceramides and Platelet-Activating Factor. American Research Journal of Cardiovascular Diseases, 2 (1). https://doi.org/10.21694/2575-7601.17005