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Biomedical subjects

T Murakawa

Publications and source records attributed to T Murakawa.

At least 91 records · Page 5Linked to original sources
PubMed1987

Mg2+-Ca2+ interaction in contractility of vascular smooth muscle: Mg2+ versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels.

Contractility of all types of invertebrate and vertebrate muscle is dependent upon the actions and interactions of two divalent cations, viz, calcium (Ca2+) and magnesium (Mg2+) ions. The data presented and reviewed herein contrast the actions of several organic Ca2+ channel blockers with the natural, physiologic (inorganic) Ca2+ antagonist, Mg2+, on microvascular and macrovascular smooth muscles. Both direct in vivo studies on microscopic arteriolar and venular smooth muscles and in vitro studies on different types of blood vessels are presented. It is clear from the studies done so far that of all Ca2+ antagonists examined, only Mg2+ has the capability to inhibit myogenic, basal, and hormonal-induced vascular tone in all types of vascular smooth muscle. Data obtained with verapamil, nimopidine, nitrendipine, and nisoldipine on the microvasculature are suggestive of the probability that a heterogeneity of Ca2+ channels, and of Ca2+ binding sites, exists in different microvascular smooth muscles; although some appear to be voltage operated and others, receptor operated, they are probably heterogeneous in composition from one vascular region to another. Mg2+ appears to act on voltage-, receptor-, and leak-operated membrane channels in vascular smooth muscle. The organic Ca2+ channel blockers do not have this uniform capability; they demonstrate a selectivity when compared with Mg2+. Mg2+ appears to be a special kind of Ca2+ channel antagonist in vascular smooth muscle. At vascular membranes it can (i) block Ca2+ entry and exit, (ii) lower peripheral and cerebral vascular resistance, (iii) relieve cerebral, coronary, and peripheral vasospasm, and (iv) lower arterial blood pressure. At micromolar concentrations (i.e., 10-100 microM). Mg2+ can cause significant vasodilatation of intact arterioles and venules in all regional vasculatures so far examined. Although Mg2+ is three to five orders of magnitude less potent than the organic Ca2+ channel blockers, it possesses unique and potentially useful Ca2+ antagonistic properties.

Animals↗
PubMed1987

Pharmacokinetic evaluation of fosmidomycin, a new phosphonic acid antibiotic.

The pharmacokinetics of fosmidomycin in phase I with a total of 127 healthy male volunteers is described through single--and repeated--dose studies using oral and parenteral routes of administration. The study results indicate that fosmidomycin is well tolerated even when given in repeated doses of 8 g/day i.v. for 7 days, 4 g/day i.m. for 5 days, and 4 g/day p.o. for 7 days. The gastrointestinal absorption rate after oral dosing of 500 mg is in general about 20-40%, which can be calculated to be on average about 30% (in comparison with fosfomycin which is on average only about 11%). Absorption seems to be slow and moderate. In the single-dose studies, the mean peak serum concentrations were 2.45 micrograms/ml and 12.3 micrograms/ml after 500 mg p.o. and 7.5 mg/kg (ca. 500 mg) i.m. doses respectively. The mean concentration after 15 mg/kg (ca. 2.2 g) i.v. dose was 157 micrograms/ml at 0.25 h. The serum half-lives were 1.65 h, 1.58 h and 1.87 h after i.v., i.m. and p.o. doses respectively. The recovery rate in urine was 85.5%, 66.4% and 26% after i.v., i.m. and p.o. doses respectively. In repeated-dose studies, no serum accumulation could be observed after 1 g q6h for 5 days, 1 g q6h for 7 days or 2 g q6h for 7 days. Mean peak serum levels of 34.0-35.5 micrograms/ml were recorded at steady state. The serum protein binding found in man was less than 1%. Unmetabolized fosmidomycin was the only bioactive substance found in the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Effects of magnesium chloride on cardiovascular hemodynamics in the neurally intact dog.

To assess the cardiovascular actions of magnesium in neurally intact animals, magnesium chloride (1-4 mM/min) administered i.v., producing a peak arterial magnesium level between 4.7 and 7.2 mg/dl, was given to alpha-chloralose-anesthetized, open-chest dogs. Magnesium lowered heart rate by 36 +/- 11 beats/min (P less than .05), cardiac output by 0.7 +/- 0.2 liters/min (P less than .05), left ventricular (LV) peak dP/dt by 410 +/- 96 mm Hg/sec (P less than .05) and aortic and pulmonary artery pressures, but it did not change LV end-diastolic pressure, systemic resistance or pulmonary resistance. Coronary blood flow also decreased by 39 +/- 11% (P less than .05), myocardial oxygen consumption by 88 +/- 22% (P less than .05) and myocardial oxygen extraction by 53 +/- 16% (P less than .05). When heart rate was held constant, magnesium still decreased LV systolic pressure, LV peak dP/dt and coronary blood flow. The increase in serum magnesium was accompanied by an increase in serum calcium (by 1.4 +/- 0.2 mg/dl; P less than .05) and a fall in serum potassium (by 0.21 +/- 0.1 mEq/l), but not by a change in serum sodium, myocardial electrolyte arteriovenous differences or arterial pH. Thus, at blood concentrations that are observed in humans after therapeutic dosages of magnesium, a depression of cardiac performance is observed in the anesthetized dog. Although magnesium produces a fall in coronary blood flow, this appears to be due at least in part to a decrease in myocardial oxygen requirements because myocardial oxygen extraction also decreases. Rapid changes in serum electrolytes accompany these hemodynamic effects.

Animals↗