Positive inotropic effect of purified green tea catechin derivative in guinea pig hearts: the measurements of cellular Ca2+ and nitric oxide release.

Each individual and pure catechin isolated from green tea was investigated as to its myocardial or blood pressure effects. The nitric oxide (NO) electrode and fluorometry were used to monitor changes in the NO and Ca(2+) contents of the heart, together with simultaneous recordings of the left ventricular developed pressure. The low dose of (-)-epigallocatechin-3-gallate (EGCg: 10(-6), 10(-5 )M) increased the left ventricular developed pressure with elevation of the transient fura-2 Ca(2+) signal (T(Ca)), but the high dose of EGCg (10(-4 )M) produced a maximum left ventricular developed pressure with decreases in the basal level of T(Ca) in a manner similar to the administration of the Ca-sensitizer pimobendan. However, the level of the transient NO signal (T(NO)) increased dose-dependently without any increases in the width of T(NO). In the isolated right atria, the contractile force of (-)-gallocatechin-3-gallate (GCg) at 10(-8)-10(-4 )M produced the highest pD(2) value, 6.7, in catechins (EGCg: 5.2, pimobendan: 5.1), but did not affect the heart rate. GCg, an artifact due to the epimerization of EGCg during the heating procedure, showed the most prolonged hypotensive effect in rabbits among the catechins. Each catechin (GCg or EGCg), like the NO donor, may have a therapeutic use as an NO-mediated vasorelaxant and may have an additional protective action in myocardial ischemia-reperfusion induced injury.

A role of anti-verotoxin antibody immunoreactive peptide, Virp5, from rat spinal cord.

An anti-verotoxin 2 (VT2) antibody immunoreactive 5-kDa polypeptide (Virp5), has been obtained through screening of the rat spinal cord cDNA library with the aid of anti-VT2 antibody. Virp5 was mainly expressed in the central nervous system, liver and kidney, and localized at glia-like cells and nerve fibers in the central nervous system, vascular endothelial cells and hepatic cells in the liver, as well as epithelial cells of distal tubules in the kidney. Intravenous administration of purified Virp5 elicited a dose-dependent increase in blood pressure. These results suggest that Virp5 commonly exists in the body, being partly playing a role in regulating the blood pressure.

Differences in the effects of Na+-H+ exchange inhibitors on cardiac function and apoptosis in guinea-pig ischemia-reperfused hearts.

The protective effects of the Na+-H+ exchange (NHE) inhibitors SM-198110 (2-[[(aminoiminomethyl) amino] carbonyl]-4-chloro-1H-indole-1-propanesulfonic acid monohydrate) and SM-197378 (N-(aminoiminomethyl)-1-methyl-7-(sulfooxy)-4-(trifluoromethyl)-1H-indole-2-carboxamide monohydrate) were investigated in perfused Langendorff guinea-pig hearts subjected to ischemia (40 min) and reperfusion (40 min). The recovery of left ventricular developed pressure (LVDP) from ischemia by reperfusion was 39.0% in the control, while in the hearts pretreated with SM-198110 or SM-197378 (10(-7) M), it was about 100%. The ATP level, monitored simultaneously by (31)P-nuclear magnetic resonance spectrometry, was already higher than the control value at the end of the ischemic period, and the elevation in Na+ or Ca2+ fluorometric signals induced during ischemia was suppressed. In post-treated hearts, the LVDP recovery rate was significantly higher with SM-198110 than with SM-197378. By in vitro electron paramagnetic resonance spectrometry, SM-197378 was found to directly quench the active oxygen radical, whereas SM-198110 had no effect. Numbers of apoptotic cardiomyocytes after ischemia (1 h) followed by reperfusion (5 h) were significantly lower in SM-197378-treated than in SM-198110-treated hearts, consistent with the level of activity of caspase-3. These results suggest that the antioxidant effects of NHE inhibitors have an important role in apoptosis during ischemia-reperfusion, but apoptosis is not a major manifestation of cardiac function during postischemic recovery, and that NHE-sensitive mechanisms of reperfusion injury promote both necrotic and apoptotic processes death.

Protective effects of antioxidative serotonin derivatives isolated from safflower against postischemic myocardial dysfunction.

N-(p-Coumaroyl)serotonin (C) and N-feruroylserotonin (F) with antioxidative activity are present in safflower oil. The protective effects of C and F were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. Changes in cellular levels of high phosphorous energy, NO and Ca2+ in the heart together with simultaneous recordings of left ventricular developed pressure (LVDP) were monitored by an nitric oxide (NO) electrode, fluorometry and 31P-NMR. The rate of recovery of LVDP from ischemia by reperfusion was 30.8% in the control, while in the presence of C or F a gradual increase to 63.2 or 61.0% was observed. Changes of transient NO signals (TNO) released from heart tissue in one contraction (LVDP) were observed to be upside-down with respect to transient fura-2-Ca2+ signals (TCa) and transient O2 signals detected with a pO2 electrode. At the final stage of ischemia, the intracellular concentration of Ca2+ ([Ca2+]i) and the release of NO increased with no twitching and remained at a high steady level. The addition of C increased the NO level at the end of ischemia compared with the control, but [Ca2+]i during ischemia decreased. On reperfusion, the increased diastolic level of TCa and TNO returned rapidly to the control level with the recovery of LVDP. By in vitro EPR, C and F were found to directly quench the activity of active radicals. Therefore, it is concluded that the antioxidant effects of two derivatives isolated from safflower play an important role in ischemia-reperfusion hearts in close relation with NO.