Journal of Cardiovascular Pharmacology and Therapeutics 

About: Journal of Cardiovascular Pharmacology and Therapeutics is an academic journal published by SAGE Publishing. The journal publishes majorly in the area(s): Myocardial infarction & Heart failure. It has an ISSN identifier of 1074-2484. Over the lifetime, 1307 publications have been published receiving 25384 citations. The journal is also known as: Journal of cardiovascular pharmacology & therapeutics & JCPT.

Characterization of the Adenosine Pharmacology of Ticagrelor Reveals Therapeutically Relevant Inhibition of Equilibrative Nucleoside Transporter 1

Abstract: Introduction:Studies have shown that ticagrelor has a further adenosine-mediated mechanism of action in addition to its potent inhibition of the P2Y12 receptor, which may explain some of ticagrelor’s clinical characteristics. This study aimed to further characterize the adenosine pharmacology of ticagrelor, its major metabolites, and other P2Y12 receptor antagonists.Methods:Inhibition of nucleoside transporter-mediated [3H]adenosine uptake by ticagrelor, its major metabolites, and alternative P2Y12 antagonists was examined in recombinant Madin-Darby canine kidney (MDCK) cells. The pharmacology of ticagrelor and its major metabolites at adenosine A1, A2A, A2B, and A3 receptor subtypes was examined using in vitro radioligand binding and functional assays and ex vivo C-fiber experiments in rat and guinea pig vagus nerves.Results:Ticagrelor (and less effectively its metabolites) and the main cangrelor metabolite inhibited [3H]adenosine uptake in equilibrative nucleoside transporter (ENT) 1-expressing MDCK cel...

Direct thrombin inhibitors.

Abstract: Cardiovascular disease is a leading cause of death and pathologic coagulation plays an integral role in the development, propagation, and intervention of cardiovascular disease. The 2 classic anticoagulants, heparin and vitamin K antagonists, though having served humanity for nearly a century, are both inconvenient and nonspecific. Through both direct and indirect roles, thrombin is essential to coagulation, and makes for a very attractive target in medical intervention of pathologic thrombosis. This article will review the nature of direct thrombin inhibitors, current indications, and ongoing trials.

Arterial elastance and wave reflection augmentation of systolic blood pressure: deleterious effects and implications for therapy.

Abstract: Systolic and pulse blood pressures are stronger predictors of stroke, coronary heart disease, myocardial infarction, heart failure, end-stage renal disease, and cardiovascular mortality than diastolic pressure. Furthermore, diastolic pressure is inversely related to coronary heart disease and cardiovascular mortality. Increased elastance (or stiffness, inverse of compliance) of the central elastic arteries is the primary cause of increased systolic and pulse pressure with advancing age and in patients with cardiovascular disease, including hypertension, and is due to degeneration and hyperplasia of the arterial wall; diastolic pressure decreases as arterial elastance increases. As elastance increases, transmission velocity of both forward and backward (or reflected) traveling waves increases, which causes the reflected wave to arrive earlier in the central aorta and augments pressure in late systole. These changes in arterial wall properties cause an increase in left ventricular afterload and myocardial oxygen consumption and a decrease in myocardial perfusion pressure, which may induce an imbalance in the supply-demand ratio, especially in hypertrophied hearts with coronary artery disease. Also, an increase in systolic pressure increases arterial wall circumferential stress, which promotes fatigue and development of atherosclerosis. Vasodilator drugs have little direct active effect on large elastic arteries but can markedly reduce wave reflection amplitude and augmentation index by decreasing elastance of the muscular arteries and reducing pulse wave velocity of the reflected wave from the periphery to the heart. This decrease in intensity (or amplitude) and increase in travel time (or delay) of the reflected wave causes a generalized decrease in systolic pressure and arterial wall stress and an increase in ascending aortic flow during the deceleration phase. The decrease in systolic pressure brought about by this mechanism is grossly underestimated when systolic pressure is measured in the brachial artery.

Ticagrelor Inhibits Adenosine Uptake In Vitro and Enhances Adenosine-Mediated Hyperemia Responses in a Canine Model:

Abstract: Aims: A routine secondary pharmacology screen indicated that reversibly binding oral P2Y12 receptor antagonist ticagrelor could inhibit adenosine uptake in human erythrocytes, suggesting that ticagrelor may potentiate adenosine-mediated responses in vivo. The aim of this study was to further characterize the adenosine uptake inhibition in vitro and study possible physiological consequences of adenosine uptake inhibition by ticagrelor in an anesthetized dog model of coronary blood flow compared to dipyridamole. Methods and Results: We measured [2-3H]adenosine uptake in purified human erythrocytes and several cell lines in the presence of ticagrelor or the known uptake inhibitor dipyridamole as a comparator. Using an open-chest dog model (beagles), we measured the left anterior descending (LAD) coronary artery blood flow during reactive hyperemia after 1 minute occlusion or intracoronary infusion of adenosine before and after administration of vehicle, ticagrelor, or dipyridamole (each n = 8). Ticagrelor co...

Metabolic Syndrome: Clinical and Policy Implications of the New Silent Killer

Abstract: The United States is experiencing its greatest life expectancy ever. Nonetheless, the general health of the US population is far from at an all-time high. An important contributor to the pandemic o...