Effects of beraprost on the transmembrane potentials of guinea-pig ventricular muscles during normoxia and hypoxia-reoxygenation.

1. The present study was performed to determine whether beraprost, a new stable analogue of prostacyclin, may exert beneficial effects on the transmembrane action potentials during normoxia and hypoxia-reoxygenation in isolated right ventricular muscles of the guinea-pig. 2.

BMPs induce direct bone formation in ectopic sites independent of the endochondral ossification in vivo.

Bone formation in vivo occurs via two major processes, one of which depends on pre-existing cartilage, and the other does not. Bone morphogenetic proteins (BMPs) have been suggested to induce cartilage formation from non-skeletogenic mesenchymal cell population, which results in osteogenesis through the endochondral sequence. In the present study we examined if BMPs could cause direct bone formation independent of pre-existing cartilage using bovine fibrous collagen membrane (FCM) as a carrier for BMPs.

Effects of long-term oral administration of NZ-105, a novel calcium antagonist, with or without propranolol in spontaneously hypertensive rats.

A new calcium antagonist, NZ-105 ((+/-)-2-[benzyl(phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2-yl)-4- (3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethanol) (10 mg kg-1, p.o.), showed slow-onset hypotensive effect in spontaneously hypertensive rats (SHRs).

Inotropic effects of ryanodine and calcium antagonists on embryonic and hatched chick myocardium.

Effects of extracellular Ca2+ and inotropic agents on contractile force were examined in myocardial preparations from embryonic and hatched chicks. Measurement of contractile force was performed in an organ bath with whole hearts for the young embryo (5 to 6 days old) and with isolated strips from the right ventricles for the old embryos (16 to 18 days old), hatched chicks (within 24 hours after hatching) and 1 week old chicks. The extracellular Ca2+ concentration-contractile force curve was in a lower concentration range in young embryonic hearts when compared with older ones.

Studies on the hypotensive mechanisms of NZ-105, a new dihydropyridine derivative, in rats and rabbits.

1. Intravenous administration of NZ-105 caused a slow-onset and long-lasting hypotension in anesthetized SHR. 2.

Possible action of cyclopiazonic acid on myocardial sarcoplasmic reticulum: inotropic effects on neonatal and adult rat heart.

Cyclopiazonic acid (CPA), a mycotoxin from Aspergillus and Penicillium, has been described as a highly selective inhibitor of Ca(2+)-ATPase in the sarcoplasmic reticulum (SR) in skeletal and smooth muscles but no reports at present deal with the effect of CPA in cardiac muscle. In the present study, we examined the inotropic effect of CPA on adult and neonatal rat myocardia, the contractions of which are known to be highly dependent on Ca(2+)-release from the sarcoplasmic reticulum and transsarcolemmal Ca(2+)-influx, respectively. CPA (30 microM) produced a negative inotropic effect in adult preparations, accompanied by marked prolongation of the contraction duration.

Hypotensive effect of bopindolol in pithed rats.

1. Effects of bopindolol, a beta adrenoceptor antagonist with partial agonist activity, on the diastolic blood pressure and heart rate of pithed rats were compared with those of pindolol. 2.

Positive chronotropic and inotropic responses to lysophosphatidylcholine are mediated by norepinephrine released from myocardial sympathetic nerve terminals.

1. The effects of beta-adrenoceptor blockade and reserpinization on the positive chronotropic and inotropic responses to lysophosphatidylcholine (LPC) were examined in isolated atrial and ventricular preparations from rat hearts. 2.

Localization of bone morphogenetic protein-induced bone and cartilage formation on a new carrier: fibrous collagen membrane.

A fibrous collagen membrane (FCM) made of crosslinked reconstituted collagen fibers was applied as a carrier of BMP. The effectiveness of FCM as a BMP carrier was compared with conventionally used insoluble bone matrix (IBM). Partially purified BMP was obtained from a guanidine HCl extract of bovine bone after a three-step chromatographic procedure.

Effect of Mn2+ on neonatal and adult rat heart: initial depression and late augmentation of contractile force.

In the present study, we examined the inotropic effect of Mn2+ on adult and neonatal rat myocardia, contraction of which is known to be highly dependent on Ca2+ release from the sarcoplasmic reticulum and trans-sarcolemmal Ca2+ influx, respectively. Mn2+ produced an initial negative inotropic effect followed by a late augmentation of contractile force in both neonatal and adult preparations, accompanied by marked prolongation of the contraction duration. The attenuation of the late augmentation by ryanodine was greater in the adult while the effect of nicardipine was greater in the neonate, which was similar to the effects of the two drugs in the absence of Mn2+.

Cardiac and vascular effects of NZ-105, a novel dihydropyridine derivative, in vitro.

The cardiovascular selectivity of NZ-105, a novel dihydropyridine derivative, was studied in vitro in comparison with nicardipine and other calcium antagonists. NZ-105 and nicardipine (10(-9), 10(-8) M) decreased the spontaneous contraction rate of the isolated guinea-pig right atrium. On the other hand, NZ-105, even at concentrations as high as 10(-6) M, slightly diminished the contractile force of the electrically driven left atrium, while nicardipine strongly and dose-dependently decreased the contractile force at a concentration of 10(-7) M by 39.

Action potential shortening and negative inotropic effects of a novel potassium channel opener, NIP-121, as compared with cromakalim in guinea pig ventricular myocardium.

The potencies of NIP-121, a new potassium channel opener, to shorten action potential duration and to decrease the contractile force was examined using isolated guinea pig right ventricular free wall and papillary muscle preparations, respectively; and they were compared with those of cromakalim. NIP-121 was about 10 times more potent than cromakalim with respect to both effects. This potency ratio in cardiac muscle was about the same as that observed in rat aorta and portal vein.

The antihypertensive property of NIP-121, a novel potassium channel opener in rats.

The antihypertensive effects of NIP-121, a novel potassium channel opener, were examined in comparison with cromakalim and its active enantiomer, lemakalim. In experiments by direct blood pressure measurements, orally administered NIP-121 dose-relatedly decreased arterial blood pressure in conscious spontaneously hypertensive rats (SHRs), and the ED20 values (the doses to produce 20% decrease of the mean blood pressure) of NIP-121 and cromakalim were 0.010 and 0.

Vasorelaxing and receptor binding properties of NZ-105, a novel dihydropyridine derivative, in isolated rabbit aorta.

The vasorelaxing and dihydropyridine receptor binding properties of NZ-105, a new dihydropyridine derivative, were studied using isolated rabbit aorta, and compared with those of nicardipine, nifedipine and diltiazem. NZ-105 (3 x 10(-10)-3 x 10(-9) M), nicardipine (3 x 10(-10), 10(-9) M), and diltiazem (3 x 10(-7), 10(-6) M) selectively relaxed aortic strips precontracted with high-K+ solution (50 mM) with little effect on strips precontracted with phenylephrine (10(-5) M) or clonidine (10(-6) M). The relaxation produced by NZ-105 was of very slow onset, and no recovery was observed after a 2 hr washout with high-K+ or normal bathing solution.

Potassium channel opening properties of a novel compound, NIP-121, cromakalim and nicorandil in rat aorta and portal vein.

A novel compound, NIP-121, cromakalim and nicorandil caused concentration-dependent relaxation of rat aortas precontracted with 30 mM KCl, with pEC50 (M) values of 8.2, 7.1 and 5.

Rat heart organ culture for the study of trophic substances involved in the maintenance of normal sensitivity to norepinephrine: possible involvement of cAMP and search for other factors.

In organ culture conditions, in the absence of in vivo factors, the newborn rat right atria acquire a high sensitivity to agonists similar to that seen before sympathetic innervation and after denervation. In the present study, we examined the effects of various extracts and substances on the development of supersensitivity to norepinephrine (NE) to obtain information on the in vivo factors that regulate myocardial sensitivity. Addition of rat serum, right atrial extract, superior cervical ganglionic extract, vas deferens extract, carbachol, insulin, cortisone, thyroxin, and neuropeptide Y in the culture medium did not prevent the development of supersensitivity.

[Electrocardiogram in pulmonary heart disease--clinical evaluation of right chest leads].

A clinical study was made to evaluate the usefulness of electrocardiograms in right precordial leads (V3r or V4R) for the diagnosis of cardiac complications among patients with chronic pulmonary disease. Walsh and colleagues reported that the change of direction in the terminal vector of QRS loop in the vector cardiogram is useful for the evaluation of chronic pulmonary heart disease. They showed that the terminal vectors of QRS loops tend to deviate to the right and/or posterior direction in the early stage of chronic pulmonary heart disease.

Role of beta-adrenoceptor-adenylate cyclase system in the developmental decrease in sensitivity to isoprenaline in foetal and neonatal rat heart.

1. The inotropic and chronotropic sensitivity to noradrenaline and isoprenaline (Iso) of foetal and neonatal rat heart decreases as the heart becomes sympathetically innervated. In the present study, we have examined adenylate cyclase (AC) activation and beta-adrenoceptor binding to determine whether a developmental decrease in sensitivity was demonstrable in the beta-receptor-AC system of atrial and ventricular membranes from the 15 day foetus and 1 day and 7 day neonates.

Antihypertensive and diuretic effects of NZ-105, a novel dihydropyridine derivative.

Studies on the antihypertensive and diuretic actions of NZ-105, a new dihydropyridine derivative, were performed in comparison with nicardipine. NZ-105 and nicardipine (5, 10 and 20 mg/kg, p.o.

Effect of ryanodine on neonatal and adult rat heart: developmental increase in sarcoplasmic reticulum function.

Negative inotropic responses to nicardipine, MnCl2 and ryanodine of isolated papillary muscles were compared between 1-day-old neonatal and adult rats. All of the drugs produced dose-dependent negative inotropic responses at both ages. Nicardipine and MnCl2 were effective at lower concentrations in the neonate when compared to the adult, while ryanodine was more effective in the adult.

Endothelium-dependent vasodilator effects of platelet activating factor on rat resistance vessels.

1. To elucidate the mechanisms of the powerful and long-lasting hypotension produced by platelet activating factor (PAF), its effects on perfusion pressure in the perfused mesenteric arterial bed of the rat were examined. 2.

Developmental increase in the inotropic and cyclic AMP response to isoproterenol in embryonic and newly hatched chicks.

The cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels of ventricles isolated from 15- to 20-day-old chick embryos and 0- to 3-day-old hatched chicks were compared to clarify the mechanism underlying the change in sensitivity to isoproterenol during perinatal developmental stages when the functional sympathetic innervation has been completely achieved. Isoproterenol produced a positive inotropic effect on ventricles isolated from both embryonic and hatched chicks, but the ventricles from the hatched chicks were more sensitive. At both developmental stages sotalol was an equipotent antagonist of isoproterenol.

Platelet-activating factor: lack of direct action on guinea pig myocardium and possible transmitter release from cardiac sympathetic nerve endings at high concentrations.

Microelectrode and mechanical studies were performed with isolated guinea pig myocardium (right ventricular free walls and papillary muscles) to examine the effects of platelet-activating factor (PAF) and lysophosphatidylcholine (LPC). Low concentrations of PAF (10(-8) to 10(-6) M, a range equivalent to the blood concentrations that produce marked hypotension in vivo) had no effects on action potential configuration and contractile force. High concentrations (10(-5) to 10(-4)M) of PAF and LPC per se elicited slow response action potentials with concomitant contraction (restored contraction) in the myocardium depolarized with elevated K+ (25 mM); they also augmented slow responses and restored contractions produced by a low concentration of isoproterenol (10(-8) M).

Altered responsiveness to autonomic transmitters of hearts from neonatal spontaneously hypertensive rats.

Responsiveness to autonomic neurotransmitters of isolated hearts from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were compared in 1-day-old and 4-week-old neonates and adults. Chronotropic responses to norepinephrine (NE) and acetylcholine (Ach) were examined using right atrial preparations. There was no difference in the basal beating rate between SHR and WKY at all ages tested.

Kinetic analysis of the positive inotropic action (PIA) of ouabain in isolated perfused rabbit heart. Slow onset of PIA and slow binding to Na+, K+-adenosine triphosphatase.

The positive inotropic action (PIA) of ouabain was analyzed kinetically using isolated perfused rabbit heart. The input function of the ouabain concentration in the perfusate (Ci) into the heart was controlled by changing the volume of the reservoir and the rate of ouabain infusion into the reservoir fixed in front of the heart. The time courses of PIA were measured continuously with different infusion rates.