Vasorelaxation induced by dodoneine is mediated by calcium channels blockade and carbonic anhydrase inhibition on vascular smooth muscle cells.

publicationInternational audienceDodoneine (Ddn) is one of the active compounds identified from Agelanthus dodoneifolius (DC.) Polhill and Wiens, a medicinal plant used in traditional medicine for the treatment of hypertension. This dihydropyranone exerts hypotensive and vasorelaxant effects on rats, and two molecular targets have been characterized: the carbonic anhydrase and the L-type calcium channel in cardiomyocytes with biochemical and electrophysiological techniques, respectively. To further evaluate the involvement of these two molecular targets in vasorelaxation, the effect of Ddn on rat vascular smooth muscle was investigated. The effects of Ddn on L-type calcium current and on resting membrane potential were characterized in A7r5 cell line using the whole-cell patch-clamp configuration. The molecular identities of carbonic anhydrase isozymes in smooth muscle cells were examined with RT-PCR. Vascular response was measured on rat aortic rings in an organ bath apparatus and the effect of Ddn on intracellular pH was determined by flow cytometry using the pH-sensitive fluorescent probe BCECF-AM [2,7-Bis-(2-Carboxyethyl)-5-(and-6)-Carboxyfluorescein, Acetoxymethyl Ester]. 100µM Ddn reduced calcium current density of about 30%. In addition, carbonic anhydrase II, III, XIII and XIV were shown to be expressed in rat aorta and inhibited in smooth muscle cells by Ddn. This inhibition resulted in a rise in pHi of about 0.31, leading to KCa channel activation, thereby inducing membrane hyperpolarization and vasorelaxation. The results of vascular reactivity experiments obtained with pharmacological tools acting on the L-type calcium current and carbonic anhydrase suggest that Ddn produces its vasorelaxant effect via the inhibition of these two molecular targets. This study demonstrates that Ddn induced vasorelaxation by targeting two proteins involved in the modulation of excitation-contraction coupling: L-type calcium channels and carbonic anhydrase

Nuclear internal conversion between bound atomic states

We present experimental and theoretical results for rate of decay of the (3/2)+ isomeric state in $^{125}$Te versus the ionic charge state. For charge state larger than 44 the nuclear transition lies below the threshold for emission of a K-shell electron into the continuum with the result that normal internal conversion is energetically forbiden. Rather surprisingly, for the charge 45 and 46 the lifetime of the level was found to have a value close to that in neutral atoms. We present direct evidence that the nuclear transition could still be converted but without the emission of the electron into the continuum, the electron being promoted from the K-shell to an other empty bound state lying close to the continuum. We called this process BIC. The experimental results agree whith theoretical calculations if BIC resonances are taken into account. This leads to a nuclear decay constant that is extremely sensitive to the precise initial state and simple specification of the charge state is no longer appropriate. The contribution to decay of the nucleus of BIC has recently been extended to the situation in which the electron is promoted to an intermediate filled bound state (PFBIC) with an apparent violation of the Pauli principle. Numerical results of the expected dependence of PFBIC on the charge state will be presented for the decay of the 77.351 keV level in $^{197}$Au