Cardiovascular effects of leukotrienes

Summary Leukotrienes have been shown to signif. icantly influence coronary vascular resistance, infarct size, pulmonary vascular resistance, bronchial tone, and renal vascular resistance either directly or indirectly. There is a notable dirth of data on human pathophysiologic conditions. With the advent of specific inhibitors of the synthesis and action of leukotrienes and, more importantly, of methods on the in-vivo synthesis of these potentially important mediators, these gaps in our understanding will be closed.     

Cardiovascular effects of leukotrienes

Leukotrienes are among the most potent lipid mediators of inflammation. Leukotriene B4 is one of the most potent endogenously synthesized chemotactic substances. It is probable that LTB4 plays an important role in the initial phase of the inflammatory reaction. The peptidoleukotrienes LTC4 and LTD4 are potent broncho- and vasoconstrictors. Administration of LTC4 and LTD4 leads to an increase of blood pressure in most species. These effects are sometimes dependent on the liberation of vasoactive prostaglandins. In addition, peptidoleukotrienes enhance vascular permeability rapidly. Peptidoleukotrienes elicit coronary vasoconstriction which is the most likely reason for the negative inotropic effect of these compounds. Recently the synthesis of peptidoleukotrienes has been demonstrated in the heart under experimental conditions. While the kidney shows a relatively mild vasoconstrictor response to leukotrienes, the pulmonary vascular bed generally responds with a brisk increase of resistance. Pathophysiological roles of leukotrienes require further definition. A striking increase in leukotrienes synthesis has been observed following endotoxin shock.     

Cardiovascular effects of SERM

Raloxifene has an estrogenic effect on the cardio-vascular system. In vascular endothelium, both clinical and basic studies show that raloxifene induces the synthesis and release of nitric oxide. In vascular smooth muscle, basic study shows that raloxifene attenuates the PDGF-induced cell proliferation by both induction of apoptosis and arrest of the cell cycle. We now await the results of currently ongoing prospective large scale randomized control trial, Raloxifene Use of The Heart.     

Cardiovascular effects of doping

Cardiovascular effects of doping drugs are numerous, with different mechanisms: vasoconstriction of amphetamines, erythropoietin and cocaine; sodium water retention of anabolic steroids and corticosteroids; elevation in blood viscosity of erythropoietin, perflurocarbon emulsion, recombinant hemoglobin and anabolic steroids; sympathetic nervous system activation of amphetamines, beta 2 agonists and clenbuterol; lipids profile disorder of anabolic steroids. Physical activity consequences, particularly bradycardia and dehydration, are worsening. Thrombosis and arrythmogenic effects, with possibility of sudden death, are the severe immediate events. Hypertension and coronary diseases are medium-term effects; acute myocardial infarction is frequent. Heart failure can be secondary to cardiac muscle direct fibrosis, like with anabolic steroids. These cardiovascular effects are serious and it is necessary to early detect the doping drugs use in sporstmen; all prescribing physician should be aware of existing drugs and their clinical events.     

Cardiovascular effects of Danshen

Danshen is one of the most versatile Chinese herbal drugs that have been used for hundred of years in the treatment of numerous ailments. Because of its properties of improving microcirculation, causing coronary vasodilatation, suppressing the formation of thromboxane, inhibiting platelet adhesion and aggregation, and protecting against myocardial ischemia, it is widely used either alone or in combination with other herbal ingredients for patients with coronary artery disease and other cardiovascular diseases, in both China and other countries including the United States. This article provides an overview of its history, pharmacology, pharmacokinetics, clinical applications, side effects, interactions with Western drugs, and future prospects in the management of cardiovascular diseases.     

Cardiovascular effects of airways obstruction

Airways obstruction is usually associated with substantial decreases in inspiratory and mean intrathoracic pressure (ITP). The change in ITP is correlated with the degree of inspiratory fall in arterial pressure, pulsus paradoxus. The factors influencing the degree of pulsus include venous return, afterload effects on the left ventricle (LV), diastolic ventricular interdependence, lung volume, and circulatory reflexes. I have reviewed these factors and attempted to demonstrate that their relative importance changes under different circumstances. I have discussed the importance of measuring transmural pressures to assess ventricular performance, and pointed out some possible pitfalls in the use of esophageal or pleural pressure to estimate LV surface pressure. During normal and loaded inspiration, decreased LV preload, probably related to right ventricle (RV)-LV diastolic interdependence, appears to be the primary mechanism responsible for decreased stroke volume during inspiration. During Mueller maneuvers, and possibly with severe decreases in ITP, LV afterload may be more important. When lung volume increases, as with asthma, venous return from the lower body may be a more important determinant of pulsus paradoxus. Although previous predictions that decreased ITP would lead to increased myocardial O₂ consumption were not borne out, coronary blood flow did increase with inspiratory loading. This appears to be due to a nonvagally mediated change in autonomic tone with loaded breathing. This and other reflex-mediated effects deserve more attention in future studies of stressed or abnormal inspiration. As a final point, pericardial tamponade probably leads to pulsus paradoxus by exaggerating normal diastolic right-left interactions.     

Cardiovascular effects of neuropeptide Y

Neuropeptide Y (NPY) is present in the brain, the adrenal medulla, and peripheral sympathetic nerves. This peptide is released together with catecholamines during sympathoadrenal activation. It possesses direct vasoconstrictor properties that are not dependent on simultaneous adrenergic activation. Moreover, it potentiates the vascular effect of several stimulatory substances and may contribute to the modulation of blood pressure responsiveness under a number of circumstances. NPY may also be indirectly involved in the control of blood pressure through regulating the release of hormones with well-established actions on the cardiovascular system.     

Cardiovascular effects of platelet-activating factor

Platelet-activating factor (PAF) is a unique biologically active phospholipid that is synthesized by many cells and tissues and has actions far more diverse than just platelet activation. PAF is probably a mediator of the normal inflammatory and thrombotic responses. Inappropriate or excessive production of PAF can lead to vascular injury, particularly via its proinflammatory effects, and marked hemodynamic derangements. There is evidence that PAF may play a role in clinical syndromes of shock, infarction, and reperfusion injury. Antagonists of the PAF receptor have been developed and have therapeutic potential in these common life-threatening disorders.