Endothelial dysfunction in Coronavirus disease 2019 (COVID-19): Gender and age influences.

Several risk factors are associated with a worse outcome for COVID-19 patients; the most recognized are demographic characteristics such as older age and male gender, and pre-existing cardiovascular conditions. About the latter, hypertension and coronary heart disease are among the most common comorbidities recorded in infected patients, together with type 2 diabetes mellitus (T2DM). Data from Istituto Superiore di Sanità (ISS, Italy) show that more than 68.

New arylsparteine derivatives as positive inotropic drugs.

Positive inotropic agents are fundamental in the treatment of heart failure; however, their arrhythmogenic liability and the increased myocardial oxygen demand strongly limit their therapeutic utility. Pursuing our study on cardiovascular activities of lupin alkaloid derivatives, several 2-(4-substituted-phenyl)-2-dehydrosparteines and 2-(4-substituted-phenyl)sparteines were prepared and tested for inotropic and chronotropic activities on isolated guinea pig atria. Four compounds (6b, 6e, 7b, and 7f) exhibited significant inotropism that, at the higher concentrations, was followed by negative inotropism or toxicity.

Endothelium-independent vasorelaxation by ticlopidine and clopidogrel in rat caudal artery.

Objectives: Thienopyridines are prodrugs currently used as anti-aggregating agents. The aim of this study was to determine if these compounds might have vascular activity independent of hepatic bioactivation.

Methods: The direct activity of thienopyridines was studied in rat caudal arterial rings and aortic smooth muscle cells in culture.

Comparison of the binding affinity of CGP-12177A at recombinant rat alpha(1D)-adrenoceptors expressed in BHK-21 cell membranes and alpha(1)-adrenoceptors present in rat cerebral cortex membranes.

Recent in vitro studies, performed in rat aorta, mesenteric and intrapulmonary arteries, and human pulmonary artery, demonstrated that the beta-adrenoceptor ligand CGP-12177A (4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one) is also provided with antagonist or partial agonist properties at alpha(1)-adrenoceptors. These observations were supported by estimates of CGP-12177A binding affinity at alpha(1)-adrenoceptors, which have been always performed in rat cerebral cortex membranes, as a surrogate of vascular tissue. Since alpha(1D)-adrenoceptors are predominant in both rat aorta and mesenteric artery, in the present study, we measured, for the first time, the binding affinity of CGP-12177A at recombinant rat alpha(1D)-adrenoceptors expressed in BHK-21 cell membranes.

Carteolol, a non-conventional partial agonist of beta(1)-adrenoceptors, relaxes phenylephrine-constricted rat aorta through antagonism at alpha(1)-adrenoceptors.

This in vitro study was designed to investigate whether carteolol, a non-conventional partial agonists of beta(1)-adrenoceptors, relaxes phenylephrine-constricted rat aorta through activation of the low-affinity state of beta(1)-adrenoceptors or antagonist effect at alpha(1)-adrenoceptors. Carteolol-induced complete concentration-dependent relaxation of phenylephrine-contracted aorta (pD(2)=3.65+/-0.

5-HT1B receptor subtype and aging in rat resistance vessels.

The effects of 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine, and sumatriptan on rat caudal arteries were examined, with the goal of finding experimental conditions useful in enhancing the 'silent' 5-HT(1B) receptor subtype. It was shown that both reserpine treatment and K(+) depolarization increased the vasoconstriction by 5-HT receptor agonists. The role of the 5-HT(2A) receptor in vasoconstriction was examined using ritanserin (50 nmol/l), a selective 5-HT(2A) antagonist, whereas that of the 'silent' 5-HT(1B) receptor was examined using SB-224289 (0.

In vitro evidence that carteolol is a nonconventional partial agonist of guinea pig cardiac beta1-adrenoceptors: a comparison with xamoterol.

The present study was designed to verify our previous hypothesis that carteolol, a beta1/beta2-adrenoceptor-blocking agent, is a nonconventional partial agonist of cardiac beta1-adrenoceptors. To this purpose, we characterized the effects of carteolol in guinea pig myocardial preparations and measured the affinities of carteolol for high- and low-affinity sites of beta1-adrenoceptors labeled by CGP12177 [(-)4-(3-t-butylamino-2-hydroxypropoxy)-2-benzimidazol-2-one]. All experiments were performed in comparison with xamoterol, a cardioselective beta1-adrenoceptor partial agonist.

Are prostanoids related to positive inotropism by UTP and ATP?

Uridine 5'-triphosphate (UTP) and adenosine 5'-triphosphate (ATP) induce biphasic inotropic effects: first a decrease and then an increase in contractile tension were observed in isolated rat myocardial tissues. Inotropic effects were higher in atrial tissue than in ventricular or papillary muscle; thus, experiments were mostly carried out on rat atria. In this research, we mainly studied positive inotropism by using selective inhibitors of the arachidonic acid cascade.

Characterization of intrinsic sympathomimetic activity of carteolol in rat cardiovascular preparations.

We evaluated in vitro, in myocardial and vascular preparations isolated from reserpine-treated rats, the intrinsic sympathomimetic activity (ISA) of carteolol, a beta(1)/beta(2)-adrenoceptor blocking agent used in cardiovascular and non-cardiovascular diseases. In spontaneously beating atria, carteolol, at low concentrations (0.01 and 0.

Gramine: a vasorelaxing alkaloid acting on 5-HT(2A) receptors.

The vascular effects of gramine on resistance vessels were evaluated, in particular as regards the 5-hydroxytryptamine (5-HT) system. We compared the action of gramine with that of ketanserin, a 5-HT (2A) antagonist; both compounds induced concentration-dependent relaxation in precontracted arterial rings. Also, the 5-HT concentration-effect curve shifted to the right in the presence of gramine, like ketanserin.

Synthesis and pharmacological characterization of functionalized 2-pyridones structurally related to the cardiotonic agent milrinone.

A new class of cardiotonic agents characterized by a 2-pyridone structure was synthesized. Appropriate sym-2-dimethylaminomethylene-1,3-diones reacted with methylcyanoacetate to afford the desired compounds. These derivatives were evaluated for their ability in inducing cardiotonic response on guinea pig isolated myocardial preparations.