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Biomedical subjects

S Kazda

Publications and source records attributed to S Kazda.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effect of hypotensive agents on the renin-angiotensin system in vascular walls of spontaneously hypertensive rats.

Previous investigations have shown that the renin-angiotensin system (RAS) is activated in vascular walls of spontaneously hypertensive rats (SHR). The present study was undertaken to determine whether antihypertensive drugs attenuate this activation. Two calcium channel blockers, nifedipine and nitrendipine, and the diuretic muzolimine were applied to SHR for 2-4 weeks, and angiotensin (ANG) I-forming angiotensinogenase (AIFA) and ANG I converting enzyme (ACE) activities were determined. The values for both enzymes were elevated in arterial tissues of SHR (P less than 0.01), whereas in venous walls AIFA activity was decreased (P less than 0.01). All hypotensive drugs reduced arterial ACE activities in SHR (nifedipine and muzolimine: P less than 0.01; nitrendipine: P less than 0.05). Angiotensin I-forming angiotensinogenase activity was increased following treatment with nifedipine (P less than 0.01) but reduced by nitrendipine (P less than 0.05); with muzolimine, no significant alterations were observed. The results obtained indicate that in SHR, stimulation of vascular wall ACE is abolished following treatment with hypotensive agents, and the effect is independent of their mode of action. It is assumed that the activation of vascular ACE is not caused by, but rather a reaction to, elevated blood pressure.

Animals↗
PubMed1987

Calcium antagonism and protection of tissues from calcium damage.

Calcium antagonism of nifedipine, nitrendipine or nisoldipine prevented salt-induced hypertension, renovascular damage and mortality in Dahl salt-sensitive (S) rats. The calcium agonist BAY K 8644 accelerated the development of salt-induced hypertension in S rats. In some S rats on a low-salt diet BAY K 8644 induced renovascular damage without sustained hypertension. In stroke-prone spontaneously hypertensive rats (SHRSP) on a normal diet the natural appearance of stroke was correlated with an increased calcium content in brain and kidney tissue. Nimodipine prevented stroke and the increase in brain calcium content without affecting the high blood pressure. A similar protective effect without substantial influence on high blood pressure was achieved by bilateral parathyroidectomy. Hypertension-associated vascular damage does not necessarily depend on the systemic intravascular pressure. In malignant hypertension the deleterious calcium overload in tissues may be activated or inhibited independently of the regulation of arterial blood pressure.

Animals↗
PubMed1987

Role of nisoldipine on blood pressure, cardiac hypertrophy, and atrial natriuretic peptides in spontaneously hypertensive rats.

The effect of long-term treatment with the calcium antagonist nisoldipine on development of hypertension, cardiac hypertrophy, and plasma levels of atrial natriuretic peptides (ANP) was determined in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) of the same age. Measurement of immunoreactive ANP in plasma provided a sensitive marker for the severity of hypertension and the associated cardiac overload. Long-term treatment with nisoldipine prevented the development of hypertension, the associated heart failure, and the increase of plasma levels of ANP in SHR but had no effect on systolic blood pressure, heart weight, and plasma levels of ANP in WKY. In addition, nisoldipine had a therapeutic effect in old SHR with manifest cardiac failure in end-stage hypertension, as evidenced not only by the reduction of blood pressure but also by the reduction of cardiac hypertrophy, of elevated immunoreactive ANP in plasma, and of increased plasma renin activity.

Animals↗
PubMed1987

Nifedipine corrects the blunted renal response to saline loading in hypertension-prone SBH rats.

The elimination of an acute oral saline load is markedly blunted in adult Sabra hypertension-prone (SBH) rats compared with hypertension-resistant Sabra normotensive (SBN) rats. Within 2 h, urinary output and the excretion of sodium and potassium are significantly reduced, while urine osmolality is markedly elevated in SBH rats. The long-term administration of nifedipine, 20-30 mg/kg body weight enhanced the diuretic and natriuretic response to saline loading in members of both strains. The effect was significantly more pronounced in SBH, especially in adult animals where the diuretic and natriuretic response averaged 150 and 130% of control, while in SBN the enhanced response was 50 and 20%, respectively. As a result of the disparate effect of nifedipine in the two strains, the blunted response of SBH was abolished. The mechanism of the preferential response to nifedipine of SBH rats remains to be determined.

Animals↗
PubMed1987

Renal effects of 1,4-dihydropyridines in animal models of hypertension and renal failure.

Renal effects of 1,4-dihydropyridine (DHP)-type calcium antagonists (nitrendipine and nisoldipine) were analyzed in diverse conditions, such as long-term antihypertensive treatment, acute saline-loading, and acute renal failure in rats. In spontaneously hypertensive rats (SHR), 60-week treatment with nitrendipine resulted in normotensive blood pressure values without increasing body weight, an indicator of salt-water retention, or increasing plasma renin activity and plasma aldosterone concentration compared with the untreated rats. After acute saline-loading of normotensive or hypertensive rats, administration of calcium antagonists nitrendipine and nisoldipine increased urinary volume and sodium excretion. This was in contrast to the effects observed with the vasodilator minoxidil, with which salt-water retention was shown. In acute renal failure induced by 60-min renal ischemia in uninephrectomized rats, administration of nisoldipine decreased mortality rate and improved kidney function. The increase in renal tissue calcium content and the decrease in ATP content associated with the renal failure was abolished by nisoldipine treatment. In conclusion, renal protective effects are present with DHP-type calcium antagonists; however, mechanisms in situations such as hypertension or acute renal failure might be different and deserve further analysis.

Acute Kidney Injury↗
PubMed1987

Blockade of the response to volume expansion by monoclonal antibodies against atrial natriuretic peptides.

It is known that plasma levels of atrial natriuretic peptides (ANP) increase in response to volume expansion. However, the extent to which these increased levels of ANP participate in the renal response to volume expansion remained unknown. This question can be answered with the aid of a monoclonal antibody that binds specifically to the biologically active forms of ANP: Ascitic fluid containing this monoclonal antibody dose-dependently and specifically blocks the natriuretic, diuretic and hypotensive effects of synthetic atriopeptin II given intravenously in rats. Volume expansion induced by injection of 20 ml/kg homologous blood in anaesthetized rats evokes massive diuresis and natriuresis. Pretreatment with ascitic fluid containing monoclonal antibody completely blocks this diuretic and natriuretic response during the first 20 min after volume expansion. Thus the initial renal response to volume expansion is due to the increase in endogenous ANP. Similar results were obtained for volume expansion with isotonic saline in conscious rats. It is supposed that the effects of ANP are mediated through particulate guanylate cyclase activation and intracellular cyclic guanosine-monophosphate (cGMP) accumulation in target tissues including renal and vascular smooth muscles cells. Besides increasing plasma ANP levels (measured by radioimmunoassay) volume expansion also induces an increase of cGMP levels both in plasma, urine and in renal tissue. This increase is ANP-dependent as it can be blocked by the monoclonal antibody.

Animals↗
PubMed1986

Effects of nitrendipine on vascular integrity.

Ongoing investigations with vasodilating drugs have established their antihypertensive efficacy. Nitrendipine, a new calcium channel blocker and vasodilator, not only decreases blood pressure but also has a tissue-protective effect that improves impaired renal function and prevents generalized vasculopathy in hypertensive animals. In addition, nitrendipine appears to preserve tissue integrity in both prophylaxis and therapy. These findings suggest that the development of vascular lesions and target organ damage associated with hypertension are not due merely to high intravascular pressure, but that some additional factors such as cellular calcium overload may be involved.

Animals↗
PubMed1986

The elevation of cyclic GMP as a response to acute hypervolemia is blocked by a monoclonal antibody directed against atrial natriuretic peptides.

Substantial volume expansion in conscious rats induces a strong diuresis and natriuresis that is caused by the increase in plasma levels of atrial natriuretic peptides (ANP) as measured by a radioimmunoassay. This renal response could be blocked by monoclonal antibodies directed against ANP. Parallel to the change in ANP, the cyclic GMP levels in plasma, urine and kidney tissue were increased after volume loading and reduced after additionally given antibodies. From this study it seems to be clear that the cyclic GMP rise is not a direct effect of volume expansion but is specifically mediated by the released ANP.

Animals↗
PubMed1985

Salt-induced hypertension in the 'Sabra' rat strain: influence of nifedipine treatment.

The effects of chronic dietary salt-loading and nifedipine therapy on hypertension-prone (SBH), -resistant (SBN) and parental (SB) Sabra rats were investigated. Salt diet for 12 weeks resulted in a sustained hypertension and heart hypertrophy only in SBH. Nifedipine therapy (300 p.p.m. = 300 mg/kg of food) introduced after week 7 on a salt diet, achieved small changes in salt-loaded SBN and SB rats, but resulted in a marked decrease in blood pressure in SBH rats within 1 week and in a regression of cardiac hypertrophy. Plasma renin activity rose slightly in nifedipine treated SB and SBN rats, but decreased significantly in treated SBH rats. Histopathological investigations revealed hypertensive vasculopathy in three out of nine untreated SBH rats, whereas there were no morphological changes in the treated rats.

Aldosterone↗
PubMed1985

Pharmacology of nimodipine, a calcium antagonist with preferential cerebrovascular activity.

In isolated vessels in vitro nimodipine inhibits spasms induced by depolarization independently of the vessel's origin. The spasms induced by spasmogenic agonists such as serotonin, catecholamines, histamine, thromboxane, or whole blood are inhibited only in the cerebral vessels and not in the peripheral vessels. In vivo, nimodipine inhibits cerebrovascular spasms and brain damage in acute and chronic animal experiments. In chronic studies on stroke-prone, spontaneously hypertensive rats, nimodipine prevents cerebral tissue damage and prolongs the survival time without affecting the high blood pressure. Nimodipine inhibits the transmembraneous calcium influx in the smooth muscle cells of the cerebral vessels and thus prevents cerebral hypoperfusion after spasmogenic stimulation. In chronic cerebrovascular stress nimodipine prevents harmful calcium overloading and thus ensures the integrity of the cerebral parenchyma.

Animals↗
PubMed1985

Interference of the calcium antagonist nisoldipine with the abnormal response of vessels from hypertensive rats to alpha-adrenergic stimulation.

The effects of the calcium antagonist nisoldipine on contractions stimulated by phenylephrine and B-HT 920 (agonists of alpha 1- and alpha 2-adrenoceptors) in isolated aortic rings from stroke-prone spontaneously hypertensive rats (SHRSP) and from normotensive Wistar-Kyoto rats (WKY) were investigated in vitro. Phenylephrine and B-HT 920 produced concentration-dependent contractions of vessels from both groups of animals. The absolute force of the contractions was less in the aortae from hypertensive rats after all doses of both agonists. Nisoldipine inhibited the B-HT 920-induced contraction much more in vessels from SHRSP than in those from normotensive WKY rats (IC50 = 1.5 X 10(-10) versus 7 X 10(-9) g/ml). The phenylephrine contractions were inhibited in SHRSP aortae by higher concentrations (IC50 = 8.5 X 10(-8) g/ml) of nisoldipine; in WKY, nisoldipine only produced a slight inhibition of phenylephrine-induced contractions. The inhibitory concentrations of nisoldipine on BHT-920-induced contractions are similar to those for the inhibition of the calcium or depolarization-induced contractions in other experiments. The alpha 2-agonist-induced contractions of rat aorta are dependent on transmembrane calcium supply. The higher efficacy of nisoldipine in aortae from SHRSP suggests an increased transmembrane availability of calcium ions in hypertension.

Adrenergic alpha-Agonists↗
PubMed1985

A novel 1,4 dihydropyridine, BAY K 8644, with contractile effects on vascular smooth muscle.

The effect of a new 1,4-dihydropyridine derivative, methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate, BAY K 8644, was studied on isolated thoracic aortae obtained from male Wistar-Kyoto rats. In rat aorta BAY K 8644 had dual actions as the compound induced contractions in the concentration range 10(-8)-10(-5)M and relaxation at higher concentrations. In low concentrations (10(-8)M) BAY K 8644 increased the contractile response to both noradrenaline and potassium and shifted the concentration response curves to the left while in high concentrations BAY K 8644 (10(-4)M) had a relaxant effect on preparations precontracted by potassium. The contractile response to BAY K 8644 was resistant to wash out in drug free medium but was totally abolished in Ca-free medium. Re-addition of Ca restored the contractile response in a concentration dependent manner. BAY K 8644, 10(-6)M, shifted the Ca-concentration response curve in high potassium solution to the left and increased the maximal response. Phentolamine or propranolol had no effect neither on the contractile nor on the relaxant effect of BAY K 8644. The findings suggest that BAY K 8644 acts mainly by increasing the transmembrane influx of Ca in the vascular smooth muscle cells, and that this effect could be opposite to that of nifedipine. However, in high concentrations BAY K 8644 also seems to have a Ca-entry blocking effect.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Effects of light and BAY K 8644, a new 1,4-dihydropyridine, on mechanical responses of rat thoracic aorta.

The effect of day light and ultraviolet radiation (360 nm) on mechanical responses to BAY K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(-2-trifluoromethylphenyl)-py ridine- 5 -carboxylate), potassium (K+) and noradrenaline (NA) of rat aorta rings was investigated. The contractile response to BAY K 8644 (10(-6)M) obtained before and after exposure of the BAY K 8644 stock solution to ultraviolet radiation was unchanged and equal to that of K+, 125 mM. Ultraviolet radiation and day light did not affect responses evoked by K+ (125 mM) and NA (1.8 X 10(-5)M). In contrast to this both types of light relaxed vessels contracted by BAY K 8644 (10(-6)M). The light induced relaxations were reversible, unaffected by addition of propranolol (3 X 10(-6)M) and could not be eliminated by washing the preparations repeatedly with Krebs solution. In vessels contracted by K+ (125 mM) and NA (1.8 X 10(-5)M) ultraviolet radiation induced a reversible relaxation in the presence of BAY K 8644. BAY K 8644 (10(-4)M) and nifedipine (10(-8)M) relaxed preparations contracted by K+. Nifedipine (10(-6)M) totally relaxed preparations contracted by BAY K 8644 (10(-6)M). Ultraviolet radiation eliminated the relaxant effect of nifedipine and decreased the relaxant effect of BAY K 8644 (10(-4)M). The results indicate that BAY K 8644 is more light-stable than nifedipine and that BAY K 8644 sensitized the vascular smooth muscle to ultraviolet radiation as well as day light. Consequently this should be taken into account when BAY K 8644 is studied.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Chronic treatment with nifedipine prevents development of hypertension and abnormal red cell Na+ transport in Dahl-S-rats.

Transmembrane Na+ transport was measured in erythrocytes of salt resistant (DR) and salt sensitive (DS) Dahl rats, fed either a standard (0.4%) or high (0.8%) NaCl diet, or a high NaCl diet containing 300 ppm of the calcium entry blocker nifedipine. Whereas salt-loaded DS became severely hypertensive, those treated with nifedipine remained normotensive. With a low NaCl diet, total Na+ efflux and Na+ pump activity was lower in DS than in DR. Cotransport was more active in DS than in DR. After excess Na+ intake, total Na+ efflux was markedly reduced in DS, but normal in nifedipine-treated DS. Cell Na+ content was increased by 52% in salt-loaded DS, but not so in DS chronically treated with nifedipine. Na+ pump was completely suppressed in salt-loaded DS, but normal in DR and rats treated with nifedipine. These results suggest that Na+ pump inhibition might be involved in the development of Dahl rat hypertension, and that prevention of salt-induced hypertension by chronic nifedipine treatment also prevents suppression of erythrocytic Na+ pump. This suggests a casual link between its biochemical and therapeutic action.

Animals↗
PubMed1985

Calcium agonism, a new mechanism for positive inotropy. Hemodynamic effects and mode of action of BAY K 8644.

BAY K 8644 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl -phenyl)-pyridine-5-carboxylate] is a nifedipine-like 1,4-dihydropyridine (DHP). In contrast to the well-known calcium antagonistic DHPs, it has vasoconstricting and positive inotropic properties. In the pentobarbital-anesthetized dog, it increases blood pressure, peripheral resistance, and left ventricular (dP/dt)max dose-dependently from 3 to 100 micrograms/kg i.v. If the vagus is blocked, heart rate is unchanged. In the isolated isovolumic perfused guinea pig heart, BAY K 8644 has positive inotropic and coronary constricting actions from 10(-9) mole/liter. At 10 times higher concentrations, this compound also increases the heart rate up to 20%. BAY K 8644 has no effect on rabbit aortic strip at physiological K+ concentrations, but potentiates the K+ -induced contraction of the strip. In the partially depolarized aortic strip (18 mM K+), BAY K 8644 induces concentration-dependent contractions, which are competitively inhibited by the calcium-antagonistic DHP nifedipine. Chemically different calcium antagonists such as verapamil or diltiazem inhibit the BAY-K-8644-induced contractions noncompetitively. These results indicate that a specific DHP receptor exists, which binds nifedipine and BAY K 8644. In contrast to the calcium-antagonistic DHPs like nifedipine, BAY K 8644 increases the calcium influx into the cell.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Influence of a calcium-enriched diet on salt-induced hypertension in rats.

Addition of dietary calcium exerts antihypertensive effects in spontaneously hypertensive rats (SHR), which can be intensified by a parallel increase of sodium in the diet. It was of interest to what extent calcium addition to a high salt diet might modify salt-dependent hypertension in salt-sensitive Dahl rats (S/JR). Groups of six S/JR and seven salt-resistant Dahl rats (R/JR) received, when 4 weeks old, diets containing differing sodium and calcium concentrations. A further group received a calcium-enriched diet supplemented with the calcium antagonist nitrendipine. A higher calcium content in the diet did not change the effects resulting from an 8% NaCl diet, with regard to heart weight and laboratory parameters. Salt-sensitive Dahl rats on a calcium-enriched NaCl diet had a more rapid development of hypertension than S/JR on a normal calcium/high salt diet or S/JR on a calcium-enriched diet supplemented with nitrendipine. Salt-resistant Dahl rats did not differ significantly with regard to blood pressure development on any diet. In contrast to the effect in SHR, dietary calcium has therefore no antihypertensive effect on salt-induced hypertension. A moderate increase in the calcium content of the diet does not alter blood pressure lowering effects of calcium antagonists.

Animals↗