The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure.

The extracellular calcium-sensing receptor CaSR is expressed in blood vessels where its role is not completely understood. In this study, we tested the hypothesis that the CaSR expressed in vascular smooth muscle cells (VSMC) is directly involved in regulation of blood pressure and blood vessel tone. Mice with targeted CaSR gene ablation from vascular smooth muscle cells (VSMC) were generated by breeding exon 7 LoxP-CaSR mice with animals in which Cre recombinase is driven by a SM22α promoter (SM22α-Cre). Wire myography performed on Cre-negative [wild-type (WT)] and Cre-positive (SM22α)CaSR(Δflox/Δflox) [knockout (KO)] mice showed an endothelium-independent reduction in aorta and mesenteric artery contractility of KO compared with WT mice in response to KCl and to phenylephrine. Increasing extracellular calcium ion (Ca(2+)) concentrations (1-5 mM) evoked contraction in WT but only relaxation in KO aortas. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared with WT, as measured by both tail cuff and radiotelemetry. This hypotension was mostly pronounced during the animals' active phase and was not rescued by either nitric oxide-synthase inhibition with nitro-l-arginine methyl ester or by a high-salt-supplemented diet. KO animals also exhibited cardiac remodeling, bradycardia, and reduced spontaneous activity in isolated hearts and cardiomyocyte-like cells. Our findings demonstrate a role for CaSR in the cardiovascular system and suggest that physiologically relevant changes in extracellular Ca(2+) concentrations could contribute to setting blood vessel tone levels and heart rate by directly acting on the cardiovascular CaSR.

Khat chewing, cardiovascular diseases and other internal medical problems: the current situation and directions for future research.

The leaves of khat (Catha edulis Forsk.) are chewed as a social habit for the central stimulant action of their cathinone content. This review summarizes the prevalence of the habit worldwide, the actions, uses, constituents and adverse health effects of khat chewing. There is growing concern about the health hazards of chronic khat chewing and this review concentrates on the adverse effects on health in the peripheral systems of the body, including the cardiovascular system and gastrointestinal tract. Comparisons are made with amphetamine and ecstasy in particular on the detrimental effects on the cardiovascular system. The underlying mechanisms of action of khat and its main constituent, cathinone, on the cardiovascular system are discussed. Links have been proposed between khat chewing and the incidence of myocardial infarction, dilated cardiomyopathy, vascular disease such as hypertension, cerebrovascular ischaemia and thromboembolism, diabetes, sexual dysfunction, duodenal ulcer and hepatitis. The evidence, however, is often based on limited numbers of case reports and only few prospective controlled studies have been undertaken. There is therefore an urgent need for more thorough case-control studies to be performed. This review outlines the current knowledge on the adverse health effects of khat chewing on the cardiovascular system and other internal medical problems, it assesses the evidence and the limitations of the studies and identifies the questions that future studies should address.