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Biomedical subjects

S Kazda

Publications and source records attributed to S Kazda.

90 records · Page 5Linked to original sources
PubMed1981

Effect of the calcium antagonist, nimodipine, on cerebral blood flow and metabolism in the primate.

The effect of the calcium antagonist nimodipine was tested in anaesthetised primates. A rapid intravenous injection of 3 or 10 micrograms kg-1 produced a transient rise in end-tidal PCO2 and a fall in arterial blood pressure, but 10 min after the injection there was no significant change in CBF. A continuous intravenous infusion of 2 micrograms kg-1 min-1 caused a modest fall in mean arterial blood pressure and an increase in cerebral blood flow (CBF), which gradually increased to 27% above control after 50 min infusion. There was no significant change in CMRO2. A continuous intracarotid infusion of 0.67 micrograms kg-1 min-1 caused an increase in CBF of between 46 and 57%. This was further increased to 87% above control after disruption of the blood-brain barrier with hyperosmolar urea. Thirty minutes after the urea, the CBF returned to 43% above control. Twenty minutes after the infusion of nimodipine had been stopped, the CBF had returned to control values. EEG studies in this group showed no obvious increase in electrocortical activity. This evidence suggests that nimodipine has no effect on cerebral metabolism but increases CBF, particularly after disruption of the blood-brain barrier.

Animals↗
PubMed1981

Pharmacological studies of the antihypertensive effect of nitrendipine.

1,4-Dihydro-2,6-dimethyl-4(3-nitrophenyl)-3,5-pyridine carboxylic acid, 3-ethyl-5-methyl ester (nitrendipine, Bay e 5009) is a new vasodilatory calcium antagonist with pronounced hypertensive efficacy. Doses of 0.3-31.5 mg/kg p.o. lower the blood pressure of rats with spontaneous, renal and desoxycorticosterone acetate (DOCA)-hypertension. Doses of 0.03-10.0 mg/kg p.o. lower the blood pressure of dogs with renal hypertension. The hypotensive effect is about 10 times less in normotensive rats. No increase in tolerance occurred during therapeutic studies lasting 5 weeks in hypertensive rats and several days in hypertensive dogs. There were no signs either of acquired tolerance developing during these studies. Dogs in fentanyl analgesia respond to i.v. administration of 0.001-0.03 mg/kg with a reduction in peripheral vascular resistance and an increase in cardiac output and heart rate. The stroke volume remains unchanged. The vasodilatory effect occurs at different degrees in different vascular beds. The most pronounced increases in vascular flow were measured in the muscular vessels of the hind quarters and in the coronary vessels. The mesenterical, skin and brain blood flows were much less affected.

Animals↗
PubMed1975

Salt and water balance and renin activity in renal hypertension of rats.

In male Sprague-Dawley rats, renal artery constriction in the presence of an inact contralateral kidney induced sodium retention (for 2-3 wk), moderate potassium loss,elevation of blood volume (BV), and an increase in water turnover. It is suggestedthat renal artery constriction activates the renin-angiotensin-aldosterone system, resulting in disordered regulation of salt and water balance and in blood pressure (BP) elevation. Subsequently, sodium balance was reestablished in one group of hypertensive rats. The previously retained sodium was kept in the body, and BV and reninactivity remained elevated. In a second group of animals, a malignant course of hypertension developed: BP surpassed a critical level of about 180 mmHg; sodium, potassium, and water were lost; BV declined; renin activity was further stimulated; and in the contralateral kidney malignant nephrosclerosis occurred. It is assumed that pressure diuresis and natriuresis induce a vicious circle: the increasing renin activity may maintain or further increase BP level, therby inducing further salt and water loss, etc.; high BP levels and high renin activities induce vascular damage and deterioration of renal function.

Adrenal Glands↗
PubMedDate not supplied

Protection against cardiac anoxia--role and limitations of increased glycogen reserves in the isolated rat right ventricular strip.

The effects of drugs on rat cardiac glycogen reserves in vivo, and on the subsequent in vitro sensitivity of the right ventricular strip preparation to anoxia have been investigated. Isoproterenol (0.2 mg/kg i.p.) causes immediate cardiac stimulation and reduction of glycogen reserves, coupled with an increased susceptibility to anoxia. Several hours after administration, glycogen levels are found to be greatly (100-200%) increased, by a "supercompensation" mechanism, and a marked tolerance to anoxia can be simultaneously demonstrated. In contrast, large doses of corticosteroids (dexamethasone, 8 mg/kg i.m.) increase glycogen levels without initial stimulation and glycogen depletion; increased myocardial tolerance to anoxia parallels the increase in glycogen reserves in vivo. We conclude that the myocardial tolerance to anoxia in this model is related to increased glycogen reserves, which increase the rate and/or duration of anaerobic glycolysis during anoxia.

Animals↗
PubMedDate not supplied

Role of endogenous ANP on endocrine function investigated with a monoclonal antibody.

Substantial volume expansion in conscious rats induces a strong natriuresis, cyclic GMP excretion, increase in cyclic GMP in plasma and kidney tissue, decrease in plasma renin activity and plasma aldosterone concentration. These effects are directly related to an increase in plasma levels of atrial natriuretic peptides. The renal response and the changes in plasma and kidney cyclic GMP, plasma renin activity and aldosterone could be totally blocked by simultaneous administration of monoclonal antibodies directed against ANP. From this study it seems to be clear that the rise in cyclic GMP and the inhibition of the renin-aldosterone system is not a direct effect of volume expansion but is specifically mediated by the released ANP. The great importance of ANP in acute volume expansion made us wonder about the role of ANP in chronic volume expansion and under basal conditions without volume loading. Chronic volume loading was induced pharmacologically by the sodium retaining vasodilatator minoxidil. Under both chronic volume expansion and basal conditions the neutralization of the circulation ANP by antibody administration leads to reduced plasma cyclic GMP levels. No alterations in urinary sodium excretion, plasma renin activity and plasma aldosterone concentration could be observed: In conclusion, the monoclonal antibody directed against ANP is a useful tool for the investigation of the physiological role of endogenous ANP.

Aldosterone↗
PubMedDate not supplied

Influence of nifedipine on ventricular function and myocardial hypertrophy in spontaneously hypertensive rats.

We compared left ventricular (LV) hemodynamics, LV muscle mass (LVMM), and LV geometry of 13 spontaneously hypertensive rats (SHRs) treated for 20 weeks with nifedipine (30 mg/kg/day) with those of 11 age-matched untreated SHRs. LVMM, LVMM related to end-diastolic volume (LVMM/EDV), LV pressure (PLV), systolic wall stress (Tsyst), ejection fraction (EF), cardiac index (CI), and isovolumetric contractility indices (dP/dtmax, IP, t-dP/dtmax, and VCE) were determined. Nifedipine treatment lowered PLV from 170 to 136 mm Hg and Tsyst from 222 to 194 10(3) dyn/cm2. LVMM and LVMM/EDV decreased moderately from 800 to 744 mg and from 2.56 to 2.29 mg/microliter, respectively. Left ventricular ejection was markedly increased (EF from 52 to 64%; CI from 154 to 178 ml/min X kg), whereas isovolumic contractility indices remained unchanged. Thus, nifedipine reduced but did not totally prevent myocardial hypertrophy and enhanced LV function. These effects seem to result from reduction in LV afterload and not from altered myocardial contractility.

Animals↗
PubMedDate not supplied

The renal response to acute hypervolemia is caused by atrial natriuretic peptides.

In anesthetized rats, synthetic rat atriopeptin II produced an increase in urinary volume and sodium excretion as well as a decrease in arterial blood pressure. Both the natriuretic and hypotensive effects were blocked by monoclonal antibodies directed against atriopeptin II. The diuresis and natriuresis caused by furosemide was not inhibited by these antibodies. Thus, the monoclonal antibodies provide a specific inhibitor for atriopeptin-mediated responses in vivo and can be used to investigate the role of atriopeptin in volume regulation. Volume expansion with 20 ml/kg i.v. homologous blood induced strong diuresis and natriuresis in the anaesthetized rat. This response was also blocked by the described monoclonal antibodies. A radioimmunoassay for the determination of atriopeptin-like immunoreactivity (ANP-IR) is described. The plasma levels of ANP-IR 8 min after blood injection were 3-4 times higher than in control rats. Thus, the strong diuresis observed after volume expansion is due to an increase in circulating atrial natriuretic peptides that obviously exert a regulative function in fluid volume control.

Animals↗
PubMedDate not supplied

Factors involved in the antihypertensive action of calcium antagonists.

The main mechanism underlying the antihypertensive action of calcium antagonists is believed to be the vasodilation of peripheral vessels. To compare the effects of calcium antagonists with those of other vasodilators, nifedipine or its antihypertensive analog nitrendipine were tested in different normotensive and hypertensive rat strains and situations. The acute blood-pressure-lowering effect of nifedipine in the Dahl salt-sensitive rat was characterized by a rapid onset of action, the minimal effective oral dosage (0.1 mg/kg) being effective for up to 6 hours. Nifedipine was approximately 3 times more potent than hydralazine and equipotent to, but of shorter duration of action than, minoxidil. Natriuretic activity in normotensive Wistar and hypertensive Dahl salt-sensitive rats was observed with nitrendipine after an acute saline load (30 ml/kg by mouth), whereas vasodilators such as minoxidil and hydralazine decreased renal function under these conditions. Treatment of spontaneously hypertensive rats (SHR) with nifedipine in food (315 parts per million) for 60 weeks prevented the development of hypertension and resulted in decreased plasma renin activity and plasma aldosterone concentration in comparison to untreated SHR controls. Moreover, absolute and relative heart weights were reduced in the treated rats. Results suggest that the antihypertensive action of calcium antagonists, at least those of the dihydropyridine type, is not only due to peripheral vasodilation, since in contrast to other vasodilators a hyperdynamic circulation is not induced, the renin-angiotensin-aldosterone system is not activated, and sodium/volume retention cannot be expected because of a primary natriuretic effect. Therefore, a reduced volume load in addition to the decrease in afterload contributes to the antihypertensive effect of calcium antagonists and their prevention of heart hypertrophy.

Aldosterone↗