Arterial stiffness is often assessed in clinical medicine, because it is not only an important factor in the pathophysiology of blood circulation but also a marker for the diagnosis and the prognosis of cardiovascular diseases. Many parameters have so far been proposed to quantitatively represent arterial stiffness and distensibility, such as pressure-strain elastic modulus (Ep), stiffness parameter (β), pulse wave velocity (PWV), and vascular compliance (Cv). Among these, PWV has been most frequently applied to clinical medicine. However, this is dependent on blood pressure at the time of measurement, and therefore it is not appropriate as a parameter for the clinical evaluation of arterial stiffness, especially for the studies on hypertension. On the contrary, stiffness parameter β is an index reflecting arterial stiffness without the influence of blood pressure. Recently, this parameter has been applied to develop a new arterial stiffness index called cardio-ankle vascular index (CAVI). Although this index is obtained from the PWV between the heart and the ankle, it is essentially similar to the stiffness parameter β, and therefore it does not depend on blood pressure changes during the measurements. CAVI is being extensively used in clinical medicine as a measure for the evaluation of cardiovascular diseases and risk factors related to arteriosclerosis. In the present article, we will explain the theoretical background of stiffness parameter β and the process to obtain CAVI. And then, the clinical utility of CAVI will be overviewed by reference to recent studies.

The inhibitory effects of cilnidipine (FRC‐8653) and various organic Ca²⁺ channel blockers on high voltage‐activated Ba²⁺ currents (HVA I_Ba) in rat sympathetic neurones were examined by means of the conventional whole‐cell patch‐clamp recording mode under voltage‐clamped conditions. HVA I_Ba was classified into three different current components with subtype selective peptide Ca²⁺ channel blockers. No ω‐Agatoxin IVA‐sensitive (P‐type) or ω‐conotoxin MVIIC‐sensitive (Q‐type) current components were observed. Most (>85%) I_Ba was found to consist of ω‐conotoxin GVIA‐sensitive N‐type components. The application of cilnidipine inhibited HVA I_Ba in a concentration‐dependent manner. The K_d value for cilnidipine was 0.8 μM. Cilnidipine did not shift the current‐voltage (I‐V) relationship for HVA I_Ba, as regards the threshold potential and peak potential where the amplitude reached a maximum. High concentrations of three hypotensive Ca²⁺ channel blockers, nifedipine, diltiazem and verapamil, all inhibited HVA I_Ba in a concentration‐dependent manner. The K_d values for nifedipine, diltiazem and verapamil were 131, 151 and 47 μM, respectively. A piperazine‐type Ca²⁺ channel blocker, flunarizine, showed a relatively potent blocking action on I_Ba. The K_d value was about 3 μM. These results thus show that cilnidipine potently inhibits the sympathetic Ca²⁺ channels which predominantly consist of an ω‐Cg‐GVIA‐sensitive component. This blockade of the N‐type Ca²⁺ channel, as well as the L‐type Ca²⁺ channel by cilnidipine suggests that it could be used therapeutically for treatment of hypersensitive sympathetic disorders associated with hypertension. British Journal of Pharmacology (1997) 122, 37–42; doi:10.1038/sj.bjp.0701342

The voltage-dependent N-type calcium channel (Cav2.2), which is distributed in the nerve endings of the central and peripheral nerves, is known to be strongly associated with the pathological processes of cerebral ischemia and neuropathic pain. Ziconotide, the chemically synthesized version of the 25-residue peptide marine toxin ω-conotoxin MVIIA, has been approved as an analgesic drug for severe chronic pain treatment. A blockade of N-type calcium channels has been suggested for reducing the neuronal injury occurring from ischemia/reperfusion events. Therefore, many efforts have been made to develop systemically available small-molecule N-type calcium channel blockers thus far. This review focuses on the latest updates concerning small-molecule N-type calcium channel blockers as potential candidates for the next generation of therapeutics for neuropathic pain and ischemic stroke. The pharmacological advantages of N-type calcium channel blockers in these pathological states are also described.

The purpose of this study was to assess the cardiovascular effects of an ultra-short-acting β-blocker, ONO-1101, by using halothane-anesthetized beagle dogs in comparison with esmolol. ONO-1101 (n = 6) or esmolol (n = 6) was administered at four infusion rates of 0.3, 3, 30, and 300 μg/kg/min. Each infusion was performed over a 30-min period, and the parameters were measured at 20-30 min after the start of each infusion. ONO-1101 significantly decreased the heart rate, rate-pressure product, left ventricular contraction, cardiac output, and relative refractory period of the right ventricle, suppressed the AV nodal conduction, and increased the effective refractory period of the right ventricle, whereas no significant change was observed in the preload and afterload of the left ventricle, intrinsic sinus nodal automaticity, His-Purkinje-ventricular conduction, and the monophasic action-potential duration of the right ventricle. The cardiovascular effects of esmolol were comparable to those of ONO-1101, except that the preload of the left ventricle was significantly increased, and the ventricular repolarization phase was shortened by 300 μg/kg/min of esmolol infusion. Meanwhile, ONO-1101 as well as esmolol significantly reduced the isoproterenol-induced increase in heart rate and ventricular contraction, but the inhibitory action of ONO-1101 was 6-8 times greater than that of esmolol. These results suggest that the suppressive effects of ONO-1101 on cardiovascular performance are significantly less potent than those of esmolol at equipotent β-blocking doses.