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Biomedical subjects

S Kazda

Publications and source records attributed to S Kazda.

At least 37 records · Page 2Linked to original sources
PubMed1990

Development of hypertension in WKY rats after transplantation of parathyroid glands from SHR/SP.

We have investigated the role of the parathyroid gland (PTG) in the long-term development of blood pressure (BP) in stroke prone spontaneously hypertensive rats (SHR/SP) and Wistar Kyoto (WKY) rats. After ablation of their own PTGs, SHR/SP animals received PTGs from WKY rats and vice versa. Transplantation resulted in a normal calcium and parathyroid hormone status without signs of hypoparathyroidism. All animals received a high salt diet (8% NaCl) for 4 weeks after transplantation of PTGs. In SHR/SP, which received PTGs from WKY, development of high BP was clearly attenuated when compared to sham-operated SHR/SP rats. WKY rats with PTGs from SHR/SP rats became hypertensive, while WKY sham-operated animals remained normotensive. PTGs from SHR/SP rats are able to induce hypertension in normotensive WKY rats.

Animals↗
PubMed1990

Influence of calcium antagonists on renal function and secondary hyperparathyroidism in acute renal failure in rats.

Glycerol-induced acute renal failure (ARF) is characterized by an increase in serum creatinine, urea, and phosphate concentration, and severe impairment of creatinine clearance. Secondary hyperparathyroidism develops rapidly during ARF. The calcium antagonist nisoldipine clearly improves renal function, which becomes evident by an improvement of creatinine clearance and attenuation of the increase of serum creatinine, urea, and phosphate concentrations. Further secondary hyperparathyroidism is ameliorated by nisoldipine treatment. In spite of normalization of the hypocalcemia in ARF by nisoldipine, weak hyperparathyroidism persists, suggesting that hypocalcemia is not exclusively responsible for elevated parathyroid hormone serum levels in ARF.

Acute Kidney Injury↗
PubMed1990

Effects of nisoldipine on atrial natriuretic peptides, blood pressure and cardiac hypertrophy in Dahl rats.

The role of the calcium antagonist nisoldipine and the arteriolar vasodilator minoxidil on plasma levels of atrial natriuretic peptides (ANP), systolic blood pressure and heart weight was estimated in inbred Dahl salt sensitive (S) rats and inbred Dahl resistant (R) rats in long-term experiments. S rats develop quickly malignant hypertension, cardiac hypertrophy and have increased ANP plasma levels when fed a high salt diet (8% NaCl), while R rats on a high salt stay normotensive. In S rats 5 weeks on a high salt diet, therapeutic treatment with nisoldipine for 5 weeks not only decreased blood pressure but also produced a regression in cardiac hypertrophy and a reduction in elevated ANP plasma levels in comparison to the untreated salt-loaded S controls. Similar results were achieved in a preventive trial. In contrast with nisoldipine, therapeutic treatment with minoxidil in salt-loaded S rats lead to no reduction in cardiac hypertrophy and produced an additional increase in plasma ANP despite a reduction in blood pressure. The increase in plasma ANP level in this model of hypertension and its modulation by antihypertensive treatment with a calcium antagonist or an arteriolar vasodilator show that the changes in ANP plasma levels are probably secondary to hypertensive disease and the associated cardiac volume overload.

Animals↗
PubMed1990

Mitogenic activity of endothelin-1 and -3 on vascular smooth muscle cells is inhibited by atrial natriuretic peptides.

The effect of endothelin-1 (ET-1) and endothelin-3 (ET-3) on the proliferation of aortic vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) was assessed by the measurement of (3H)-thymidine incorporation into DNA. ET-1 and ET-3 stimulated the DNA synthesis in a dose-dependent manner. ET-3 was less potent than ET-1 in its stimulatory activity. The increase in (3H)-thymidine incorporation is clearly attenuated by Atriopeptin III (ANP 5-28). Atriopeptin I (ANP 5-25), a ANP fragment with the reduced biological activity compared to ANP 5-28, has no effect on the endothelin mediated stimulation of DNA-synthesis.

Animals↗
PubMed1990

Therapy of diseased stroke-prone spontaneously hypertensive rats with nimodipine.

We investigated the therapeutic effect of nimodipine or parathyroidectomy in old, diseased stroke-prone spontaneously hypertensive rats by observing 98 male 1-year-old rats over 5 months. After stroke had occurred, the rats were divided into three groups: 1) parathyroidectomy, 2) nimodipine, and 3) controls. In the nimodipine group, the rats survived longer than those in the other groups. Blood pressure of the controls did not differ from the nimodipine-treated and parathyroidectomy animals. The increase in calcium content of brain and kidney tissues and of plasma renin activity, urea, and creatinine was attenuated by nimodipine or parathyroidectomy. The histology of the kidneys revealed widespread fibrinoid necrosis of arteries in all rats. In the nimodipine-treated or parathyroidectomy groups, healing of the lesions was detectable. Cerebral lesions were mainly characterized by fibrinoid necrosis. Nimodipine-treated as well as parathyroidectomied animals showed significantly fewer hypertensive cerebral lesions. In old, diseased stroke-prone spontaneously hypertensive rats, therapy with nimodipine or parathyroidectomy increased their survival rate. The cerebrovascular and renovascular lesions of treated animals were attenuated, and morphologic signs of healing were observed. Reduction of calcium overload by nimodipine or parathyroidectomy, even in an advanced stage of disease, had a therapeutic effect.

Aging↗
PubMed1989

Different effects of ANP and nitroprusside on cyclic GMP extrusion of isolated aorta.

Atrial natriuretic peptide (ANP) and sodium nitroprusside have potent vasodilator effects on the noradrenaline-precontracted isolated rabbit aorta. A distinct elevation of cyclic GMP in the aortic tissue was observed after both vasodilators. In contrast to sodium nitroprusside, ANP-(5-28) induced a dose-dependent cyclic GMP extrusion from the tissue into the medium. Thus, release of cyclic GMP appears to be specific for activation of particulate guanylate cyclase and provides a mechanism in addition to synthesis and degradation by which the cells can regulate their internal concentrations of cyclic GMP.

Animals↗
PubMed1989

Endothelin stimulates release of atrial natriuretic peptides in vitro and in vivo.

The effect of endothelin (END) on the release of atrial natriuretic peptides (ANP) was studied in isolated rat atria and in conscious rats. END stimulates the ANP release in vitro in a dose-dependent manner. An increase in ANP plasma levels and cyclic GMP plasma levels was also observed in conscious rats after injection of END. When a monoclonal antibody directed against ANP was injected together with END the increase in cyclic GMP was completely blocked. From this study it is concluded that END is a potent secretagogue for ANP both in vitro and in vivo.

Animals↗
PubMed1989

Endothelin-1-induced vascular contractions: interactions with drugs affecting the calcium channel.

Recently, a potent vasoconstrictor peptide, endothelin-1 (ET-1), was isolated from vascular endothelial cells. We investigated the inhibition of ET-1-induced contractions on isolated porcine coronary artery and rabbit aorta by calcium antagonists of the 1,4-dihydropyridine type. In addition, the vasoconstriction induced by ET-1 was compared with that induced by the calcium agonist (-)Bay K 8644. The calcium antagonists nitrendipine and nicardipine partially antagonize the vasoconstrictive effects of ET-1 in a dose-dependent manner, but this antagonism is only functional and noncompetitive. In the isolated rabbit aortic ring, ET-1 induces a half-maximal contraction. In contrast, the calcium agonist (-)Bay K 8644 has no effect on this preparation. However, when the vessels are partly depolarized by adding 15 mM K+, (-)Bay K 8644 and ET-1 express their full activity. Again here, the concentration-response curve of ET-1 is depressed by increasing concentrations of nitrendipine, but only functionally, noncompetitively. These results suggest that ET-1 acts through specific receptors different from the 1,4-dihydropyridine selective site.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Autoradiographic localization of 125J-endothelin in rat tissues.

A potent peptidergic vasoconstrictor in vitro and in vivo termed endothelin has been isolated from the supernatant of cultured endothelial cells. The autoradiographic localization of 125J-endothelin has been studied after intravenous administration in rat tissues. Highest enrichment of radioactivity was found in kidney and lung. Activity was also detected, especially in vascular wall of the aorta and adrenal gland.

Animals↗
PubMed1989

Pharmacological basis for use of calcium antagonists in hypertension.

Many different classification systems for Ca2+ antagonists were proposed. They are mostly based on structural aspects or profiles of biological activity. 1,4-dihydropyridines, with Ca2+ channel antagonistic activity, including nifedipine and nitrendipine, are highly effective as antihypertensive agents. Although Ca2+ antagonists have multiple sites of antihypertensive action, their main mechanism of action is inhibition of Ca2+ entry into the vascular smooth muscle cells. Ca2+ channel antagonists bind to specific receptors at Ca2+ channels and stabilize the channels in a mode unavailable for opening. Their effect is enhanced by depolarization of the cell membrane. Currently used pharmacological methods for detection of Ca2+ antagonistic action of drugs include: (1) inhibition of 45Ca2(+)-uptake; (2) displacement of [3H]nitrendipine from isolated membranes, and (3) inhibition of Ca2+ current in single cells or channels. Ca2+ antagonists were reported to prevent hypertension-induced vascular changes and other vascular pathology, probably related to Ca2+ overload. Vascular lesions in Dahl salt-sensitive hypertensive rats and in spontaneously hypertensive rats were prevented by chronic administration of nifedipine or nitrendipine. Hemodynamic effects of Ca2+ antagonists are characterized by reduction in total peripheral vascular resistance, increase in cardiac output, reduction in systemic left ventricular end-diastolic, pulmonary arterial and capillary wedge pressures. Ca2+ antagonists differ in potency, duration of action and their therapeutic ratios. DHPs enhance sympathetic tone and have little or no negative dromotropic action. They are, therefore, safer in combination with beta-adrenoceptor antagonists than either verapamil or diltiazem. In comparison with other Ca2+ antagonists nitrendipine is highly potent as a vasodilator. As a negative inotropic agent, it is, however, less potent than either verapamil or nifedipine. Nitrendipine has, therefore, a better therapeutic ratio than some of the other well-known Ca2+ antagonists. Unlike older vasodilators, e.g. hydralazine and minoxidil, Ca2+ antagonists have diuretic properties which are primarily due to inhibition of tubular reabsorption of salt and water. Under certain experimental conditions, e.g. infusion of angiotensin II, DHPs can increase GFR. Nitrendipine has also renal cytoprotective activity. It protected rats from aminoglycoside-induced nephrotoxicity and antagonized proliferative glomerular changes in nephritic rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Antihypertensive Agents↗
PubMed1988

The reduction of renin and aldosterone as a response to acute hypervolemia is blocked by a monoclonal antibody directed against atrial natriuretic peptides.

We have previously reported that the strong diuresis, natriuresis and urinary cyclic GMP excretion after acute volume loading in rats are caused by ANP and can be blocked by additionally given monoclonal antibodies directed against ANP. The present report describes that in contrast to the changes in ANP and cyclic GMP, the plasma renin activity and aldosterone concentration are decreased after volume loading. This decrease is completely blocked by simultaneous administration of the monoclonal antibodies. Plasma cyclic AMP levels are not affected. From this study it seems to be clear that the inhibition of the renin-aldosterone system is not a direct effect of volume expansion but is specially mediated by the released ANP.

Aldosterone↗
PubMed1988

Diuretic effect of nitrendipine contributes to its antihypertensive efficacy: a review.

The mechanism of the antihypertensive effect of nitrendipine is believed to be vasodilation, resulting in a reduction of the total peripheral resistance. However, in contrast to other arteriolar vasodilators, nitrendipine exerts natriuretic and diuretic effects that are more pronounced in hypertensive than in normotensive rats. In rat kidneys, nitrendipine caused a complete reversal of the decrease of glomerular filtration rate (GFR) induced by norepinephrine or angiotensin II, probably due to a selective antagonism of preglomerular vasoconstriction. A selective dilation of afferent arterioles was shown in microcirculatory studies on hydronephrotic kidneys. In normotensive rats with intact kidneys, nitrendipine increases natriuresis by inhibition of sodium reabsorption, presumably in the proximal tubuli. In normotensive humans, natriuresis was enhanced also by a primary tubular effect of nitrendipine. In hypertensive patients, an initial increase in GFR was observed; a persistent diuretic effect under chronic treatment was due to a tubular action. In spontaneously hypertensive rats (SHR), chronic treatment with nitrendipine resulted in a regression of cardiac hypertrophy in parallel with a reduction of plasma levels of atrial natriuretic peptides (ANPs), probably due to the persistent natriuretic effect. Treatment with minoxidil resulted in fluid retention, increase in ANP levels, and aggravation of cardiac hypertrophy.

Animals↗
PubMed1988

Pharmacological basis for use of calcium channel antagonists in hypertension.

The major mechanism of antihypertensive action of Ca2+ channel antagonists is the inhibition of Ca2+ entry into the vascular smooth muscle cell. Ca2+ channels are stabilized by these drugs in a mode unavailable for opening. The inhibition of Ca2+ entry leads to vasodilatation and lowering of arterial pressure. The advantages of Ca2+ channel antagonists in hypertension include improvement of blood supply to vital organs, diuretic activity, coronary vasodilatation, reduction in heart size and vascular cytoprotective effect.

Animals↗
PubMed1988

[Physiologic importance of atrial natriuretic peptide in volume expansion and hypertension: experimental studies].

The release of atrial natriuretic peptides (ANP) is stimulated by acute volume expansion. In order to elucidate the importance of the ANP release for the physiological response to volume expansion, a monoclonal antibody was used in rats. This antibody against ANP specifically blocks the ANP effects in vivo. The acute natriuresis induced by isotonic volume expansion is blocked by the antibody. However, the excretion of an additional sodium load (saline with an additional amount of 50 mmol/l sodium) is not entirely ANP-dependent. Acute volume expansion induces a dramatic decrease of plasma renin activity and a slight decrease of plasma aldosterone concentration measured 5 min after volume expansion. These effects are blocked by simultaneous administration of the monoclonal antibody. The endogenous level of ANP that can be reached in volume expansion is thus sufficient for suppression of the renin-aldosterone system. The physiological importance of ANP underlined in these volume expansion experiments raises the question of its role in pathophysiological states such as hypertension. In old, spontaneously hypertensive rats (SHR) ANP plasma levels and relative heart weights are higher than in age-matched normotensive Wistar Kyoto rats (WKY).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1987

Improved myocardial capillarisation in spontaneously hypertensive rats treated with nifedipine.

The effect of long term administration of nifedipine on myocardial capillarity was studied in spontaneously hypertensive rats. Nifedipine was given for 20 weeks, mixed into commercial rat chow (0.3 g per 1 kg). Untreated spontaneously hypertensive rats had higher arterial blood pressure and developed cardiomegaly when compared with Wistar-Kyoto rats used as controls. Nifedipine administration in spontaneously hypertensive rats lowered the arterial blood pressure and reduced cardiac weight; however, both values remained far above those for controls. Myocardial capillarity was determined using the recently introduced method of capillary domains. Hearts from untreated spontaneously hypertensive rats were characterised by greater and more variable intercapillary spacing than those from controls. The treatment of spontaneously hypertensive rats with nifedipine resulted in normalisation of morphometric indices characterising capillary spacing, probably as a result of stimulation of capillary growth as indicated by a significant decrease in myocyte to capillary ratio. Thus, despite persistent hypertension and cardiomegaly the treatment of spontaneously hypertensive rats with nifedipine restored mean intercapillary distance and index of heterogeneity of capillary spacing to normal values.

Animals↗
PubMed1987

Tissue protection by nifedipine and its calcium antagonistic derivatives in vascular damage.

Calcium ions are ubiquitous messengers of numerous cellular functions. Under normal conditions, they translate the membrane signal into specific cellular activity by electromechanical or electrosecretory coupling. An enhancement of the transmembrane calcium influx results in exaggerated cellular function, such as increased vascular contractility. Therefore, a reduction of transmembrane calcium influx by calcium antagonists effectively reduces high blood pressure (BP). It has been shown that the long-term treatment of genetically hypertensive rats with dihydropyridine calcium antagonists ameliorates the tissue damage that occurs in association with high BP in various organs. This tissue protection is not secondary to the reduction of hypertension as it can be demonstrated in the absence of BP reduction. This favourable effect may be attributed to the prevention of intracellular calcium overload which results in an exhaustion of energy-rich phosphates, excessive activation of proteolytic and phospholytic enzymes, membrane destruction and cellular death. In acute ischaemia experiments, inhibition of excessive transmembrane calcium influx by the dihydropyridine calcium antagonists prevents vascular and parenchymal damage. Moreover, long-term treatment with dihydropyridine calcium antagonists prevents vascular and parenchymatous damage in advanced or accelerated hypertension. In accordance with this concept, calcium antagonists have been shown to exert protective effects against acute ischaemic damage in both the heart and the kidney.

Humans↗
PubMed1987

Suppression of renin-angiotensin system in the heart of spontaneously hypertensive rats.

Renin-like enzyme and angiotensin converting enzyme (ACE) were identified and their specific activities measured in cardiac tissues of spontaneously hypertensive rats (SHR) and their Wistar-Kyoto (WKY) normotensive controls. In addition, the enzyme activities were determined following administration of hypotensive drugs. The pH optima of cardiac renin-like enzymes were identical with those in vascular walls, the specific activity being higher in the heart. Cardiac ACE revealed similarities with the venous wall enzyme. The highest specific cardiac renin-like activity was found in the septum and that of ACE in atria/auricles. Both enzyme values were lower in the hearts of SHR than in those of normotensive controls. Following nifedipine treatment, specific renin-like activities increased in all cardiac structures studied (P less than 0.01); with nitrendipine and muzolimine less pronounced elevations were obtained. Administration of these three hypotensive drugs resulted in a stimulation of ACE in all the cardiac structures except in atria/auricles, where their activities were lowered.

Animals↗