The Cardiovascular Effects of Methylxanthines

Abstract

In the concentration range that is normally achieved in humans, e.g., after the drinking of coffee or in patients treated with theophylline, the cardiovascular effects of methylxanthines are primarily due to antagonism of adenosine A(1) and A(2) receptors. Inhibition of phosphodiesterases or mobilization of intracellular calcium requires much higher concentrations. In conscious humans, acute exposure to caffeine results in an increase in blood pressure by an increased total peripheral resistance, and a slight decrease in heart rate. This overall hemodynamic response is composed of direct effects of caffeine on vascular tone, on myocardial contractility and conduction, and on the sympathetic nervous system. Caffeine is the most widely consumed methylxanthine, mainly derived from coffee intake. Regular coffee consumption can affect various traditional cardiovascular risk factors, including a slight increase in blood pressure, an increase in plasma cholesterol and homocysteine levels, and a reduced incidence of type 2 diabetes mellitus. Although most prospective studies have not reported an association between coffee consumption and coronary heart disease, these findings do not exclude that the acute hemodynamic and neurohumoral effects of coffee consumption could have an adverse effect in selected patient groups who are more vulnerable for these effects, based on their genetic profile or medication use.

β-Adrenergic receptors suppress Rap1B prenylation and promote the metastatic phenotype in breast cancer cells

“…However, the multiple side effects induced by theophylline, which are potentially caused by its actions as a cAMP phosphodiesterase inhibitor, 13 make theophylline a less than ideal drug for repurposing for cancer treatment. Due to the limited pharmacological options available for targeting the A 2 BR, there is a need to determine whether other GPCRs can be therapeutically targeted to regulate the participation of prenylated Rap1B in cancer.…”

Eudistomin D and Penaresin Derivatives as Modulators of Ryanodine Receptor Channels and Sarcoplasmic Reticulum Ca2+ATPase in Striated Muscle

“…Inhibition of phosphodiesterases and adenosine receptors by caffeine and other methylxanthines is known to have much higher affinity than caffeine's agonistic action on RyRs (Liu and Meissner, 1997;Bruton et al, 2003;Ishiyama et al, 2008;Francis et al, 2011;Müller and Jacobson, 2011;Riksen et al, 2011). The opposite appears to be true for MBED, as micromolar levels of MBED (found here to induce maximal activation of RyRs) had no significant effects on phosphodiesterases (Bruton et al, 2003).…”

“…In addition, caffeine, as well as other xanthines, has other cellular targets, including adenosine receptors and phosphodiesterases, which can also affect intracellular Ca 21 signaling (Zahradnik and Palade, 1993;Francis et al, 2011;Müller and Jacobson, 2011;Riksen et al, 2011).…”

Investigation of Some Pharmacological Effects of Caffeine and Taurine in Food Supplements

“…It increases blood pressure, heart rate [5] and the frequency and strength of heart contractions [6] and possesses analeptic action of the vasomotor and respiratory center in the brain [3].…”