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H Karppanen

Publications and source records attributed to H Karppanen.

At least 55 records · Page 3Linked to original sources
PubMed1989

Cardiovascular effects of L-tyrosine: influence of blockade of tyrosine metabolism.

Tyrosine is the precursor of catecholamines. Small doses of tyrosine produce tachycardia and hypertension while higher doses produce bradycardia and hypotension in anaesthetised rats. The mechanism of these effects has not been established. An increased synthesis and release of catecholamines has been suggested to be the mechanism. Various pretreatments were given to anaesthetised Wistar rats to study the influence of a blockade of L-tyrosine metabolism and thus a blockade of catecholamine synthesis, on these cardiovascular effects: valine, which inhibits tyrosine uptake into brain, alpha-methyl-p-tyrosine, which blocks the rate-limiting enzyme, tyrosine hydroxylase, carbidopa and benserazide, which both inhibit dopa decarboxylase, and desipramine, which blocks catecholamine re-uptake. Benserazide and alpha-methyl-p-tyrosine partially blocked the stimulatory effects of tyrosine. None of the pretreatments were able to block effectively the inhibitory effects of L-tyrosine. Therefore, the metabolism of tyrosine to form catecholamines may be involved in the stimulatory but not in the inhibitory cardiovascular effects of L-tyrosine. Valine pretreatment did not antagonize the depressant effects of tyrosine. Since valine blocks the uptake of L-tyrosine into the brain, the depressant effects of L-tyrosine might be peripheral rather than central in origin.

Animals↗
PubMed1989

New oral salt in treatment of high blood pressure.

The roles of sodium, potassium and magnesium in the etiology of high blood pressure are reviewed. Mechanisms of action for these cations in alterations of systemic blood pressure are discussed. A rationale for the introduction of a new Na-K-Mg salt for the prevention and treatment of hypertension in human subjects is presented. Preliminary results with this new Na-K-Mg salt are promising.

Blood Pressure↗
PubMed1988

Stimulatory effect of prostaglandin F2 alpha on gastric acid secretion in rats.

The effect of intravenously administered prostaglandin F2 alpha on gastric acid secretion was investigated in anaesthetized rats. Doses of 0.03-0.3 mg/kg PGF2 alpha stimulated gastric acid output in rats with intact vagi, whereas an inhibitory effect was observed in vagotomized animals. Treatment with 5 mg/kg of Na-meclofenamate intravenously attenuated the secretory response to PGF2 alpha, while 10 mg/kg of indomethacin intravenously and 3 mg/kg of 8-phenyltheophylline intraperitoneally were without any effect. The results indicate that intravenously administered PGF2 alpha stimulates gastric acid secretion in anaesthetized rats via activation of the vagus nerve. The effects of Na-meclofenamate and indomethacin suggest that PGF2 alpha may exert its secretagogue action via specific receptors. The lack of the effect of 8-phenyltheophylline indicates that adenosine which reportedly had a similar effect on gastric secretion after intravenous injection seems not to be involved here.

Animals↗
PubMed1987

Cardiovascular effects of L-tyrosine in normotensive and hypertensive rats.

There are conflicting reports on the blood pressure effects of tyrosine. The aim of this study was to establish complete dose-response relationships and to compare the effects of various modes of administration of L-tyrosine in anaesthetised normotensive and spontaneously hypertensive rats. The intravenous injection of L-tyrosine, 0.2-0.4 mmol/kg, produced tachycardic and hypertensive effects in both species. The higher doses (0.8-1.6 mmol/kg) produced marked bradycardiac and hypotensive responses. Intracerebroventricular administration of L-tyrosine, 0.005-0.1 mmol/kg, had no statistically significant effects. Chronic dietary administration of L-tyrosine at the approximate daily doses of 0.7-55 mmol/kg was also without any significant effects. These results suggest that the controversies in the earlier studies could be due mainly to differences in doses and modes of administration. Our results also suggest that the cardiovascular effects of tyrosine are peripheral rather than central in origin although a central site of action cannot be excluded.

Animals↗
PubMed1986

Lack of cardiovascular or ventilatory effects of melatonin in rats.

The cardiovascular and ventilatory effects of centrally and peripherally administered melatonin were examined in both normotensive rats (NTR) and in spontaneously hypertensive rats (SHR). In the experiments on anaesthetised NTR melatonin was administered intravenously at doses of 1, 10, and 100 mumol/kg, or intracerebroventricularly at doses of 0.01, 0.1, 1, and 10 mumol/kg. In the experiments on conscious SHR melatonin was administered orally at doses of approximately 2 mg per animal per day, or intracerebroventricularly at doses of 0.01, 0.1, 1, and 10 mumol/kg. Melatonin did not produce any significant cardiovascular or ventilatory effects in any of the experiments.

Administration, Oral↗
PubMed1984

Xylazine-induced sedation in chicks is inhibited by opiate receptor antagonists.

The sedative effect of xylazine and its interaction with antagonists of alpha-adrenoceptors or opiate receptors was examined in chicks. The duration of the sleep-like behavioral state induced by xylazine was determined by measuring the time interval during which the chicks failed to exhibit the righting reflex. In these chicks, intramuscular administration of xylazine (0.3-4.8 mg/kg) induced a loss of the righting reflex, the duration of which was dose-dependent. Both alpha-adrenoceptor antagonists of the alpha2 type, i.e. yohimbine (0.1-1.0 mg/kg) and compound 170150 (0.1-1.0 mg/kg) (a benzodioxane derivative), and opiate receptor antagonists, i.e. naloxone (0.4-1.6 mg/kg) and nalorphine (3.0-30.0 mg/kg), effectively inhibited the sedative effect of xylazine while prazosin (0.1-10.0 mg/kg), an alpha 1-adrenoceptor antagonist, failed to antagonize xylazine-induced sedation. These findings suggest that in addition to the stimulation of central alpha 2-adrenoceptors, activation of an endogenous opiate mechanism may be involved in the sedative effect of xylazine.

Adrenergic alpha-Antagonists↗
PubMed1984

Safety and effects of potassium- and magnesium-containing low sodium salt mixtures.

The main purpose of the present studies was to examine the safety of salt mixtures in which 35 or 55% of the NaCl in common table salt was replaced by potassium and magnesium salts. For 41 elderly hospitalized patients common salt from the hospital kitchen was replaced by Na+-K+-Mg2+ salt for 3-5 weeks; for in 85 drug-treated outpatients home use of NaCl was replaced by the use of Na+-K+-Mg2+ salt for 6 months. The patients' acceptance of the Na+-K+-Mg2+ salt was good. No metabolic or other side effects could be detected while the salt was being used. Na+-K+-Mg2+ salt was associated with a fall in blood pressure in drug-treated hypertensive patients, a rise in serum magnesium and in previously low serum potassium concentrations, a fall in raised fasting blood glucose levels, and an improvement in oral glucose tolerance. The results demonstrate that a considerable part of the NaCl in common table salt could be replaced by potassium and magnesium salts without causing potassium or magnesium toxicity. The results also lend support to the concept that an increase in potassium and magnesium intake and a decrease in sodium intake may have beneficial effects in a substantial number of people.

Aged↗
PubMed1984

Ischaemic heart disease. An epidemiological perspective with special reference to electrolytes.

Ischaemic heart disease (IHD) is a major public health problem in most industrialised countries. In the death rates from IHD, marked differences exist between various countries and also between different areas of individual countries. Unfavourable dietary factors appear to play an important role in the aetiology of IHD, and thus differences in dietary habits and the quality of food may be mainly responsible for the geographic differences in the prevalence of IHD. The present liberal use of salt as well as the refining and other industrial processing of food increase the content of sodium and decrease the content of potassium and magnesium in the diet. The high intake of sodium and the inadequately low levels of potassium and magnesium in the diet predispose to the development of arterial hypertension. Since arterial hypertension is a major risk factor of IHD, the distorted electrolyte composition of our present diet can be considered an important aetiological factor of this disease. To decrease the body burden of sodium, diuretic agents are frequently used. Unfortunately, in the presence of the relatively low content of potassium and magnesium in the diet, the diuretic-induced increases in the excretion of these electrolytes commonly decrease the potassium and magnesium levels in the body. The falls in potassium and magnesium may increase the death rate from IHD by predisposing the heart to fatal arrhythmias, and also by other mechanisms. The likelihood of magnesium deficiency also appears to be influenced by the area of residence. The higher-than-average death rates from IHD in the so-called North Karelia area in eastern Finland and in some other areas with exceptionally high death rates from this disease may be at least partly due to the very low levels of magnesium in the soil and drinking water. It can be concluded that electrolyte disturbances have important implications in the aetiology and pathogenesis of IHD.

Adult↗
PubMed1984

Effect of neuromuscular blocking drugs on arterial pressure and heart rate in rats.

The effects of neuromuscular blocking drugs on mean arterial pressure (MAP) and heart rate (HR) were studied in rats which were anaesthetised, tracheotomized and ventilated artificially. The arterial pressure was recorded from the carotid artery. Seven neuromuscular blocking drugs were injected intravenously at doses of 1, 5, and 25 mumol/kg. d-Tubocurarine, alcuronium and vecuronium lowered MAP in a dose dependent manner (maximum 40%). Succinylcholine, 1 mumol/kg, reduced MAP and HR, whereas the two larger doses increased them. Gallamine, 25 mumol/kg, or metocurine and pancuronium, 1 or 5 mumol/kg, each, induced short-lasting rises in MAP. Pancuronium, 25 mumol/kg, decreased MAP by 25%, while the largest dose of metocurine appeared to be toxic. The cardiovascular responses to neuromuscular blocking drugs were antagonized or abolished by pretreatment with the ganglionic blocking agent pentolinium. Pentolinium itself markedly reduced MAP and HR. After ganglionic blockade and restoration of MAP by noradrenaline infusion, all the neuromuscular blocking drugs induced short-lasting increases in MAP (10-30%), except d-tubocurarine which still reduced MAP by 30%, a fall which, in contrast to the effect in the absence of the pretreatments, was transient. This response to d-tubocurarine could not be abolished by a combined pretreatment with H1 and H2 antagonists showing that the hypotensive effect of this drug was not due to the liberation of histamine. These results suggest that the cardiovascular responses to neuromuscular blocking drugs in rats might be partly due to ganglionic effects. Other mechanisms are also involved since after the restoration of blood pressure by noradrenaline during the ganglionic blockade some cardiovascular responses to these drugs still occurred.

Animals↗
PubMed1984

Role of electrolytes and digitalis-like activity in hypertension: effects of digitoxin, sodium, potassium and magnesium on blood pressure.

The purpose of the present study was to test the hypothesis that an increased digitalis-like activity, induced by excessive intake of Na, is involved in the development and maintenance of hypertension. In normotensive rats prolonged administration of digitoxin alone induced only a mild and transient rise of blood pressure. Increased intake of NaCl did not affect the blood pressure of these rats. However, simultaneous administration of both digitoxin and NaCl produced a sustained elevation of blood pressure. In SHR the effect of the addition (6% of the weight of the pellets) of 1) NaCl or 2) a mixture containing 50% NaCl and 50% KCl or 3) a mixture containing 65% NaCl, 25% KCl, and 10% MgSO . 7H2O, was examined. A marked fall of blood pressure occurred during the use of the mixtures containing K and Mg. The results suggests that both an increased intake of Na and an increased digitalis-like activity are needed for the development of hypertension. The results on SHR confirm the previous findings demonstrating that the use of salt mixtures in which a part of the NaCl is replaced by K and Mg salts is beneficial compared to the use of NaCl. Furthermore, since K and Mg are effective antagonists of digitalis the results could suggest the involvement of an increased digitalis-like activity in the maintenance of hypertension.

Animals↗
PubMed1983

Synthesis and antihypertensive activity of some new quinazoline derivatives.

A series of substituted 2-piperidino-4-amino-6,7-dimethoxyquinazolines was synthesized and screened as potential antihypertensive agents. The hypotensive effect of all the new compounds was studied after intravenous administrations in urethane-anesthetized normotensive rats. The furoylpiperazine moiety in the prazosin molecule could be replaced by a more stable substituted piperidine group without loss of the blood pressure lowering activity. However, the nature of the substituent profoundly influenced the hypotensive potency as well as the duration of the hypotensive action. Some of the new compounds were found to be as potent as prazosin. On the basis of potency and the duration of the hypotensive action in the anesthetized rats, five of the most promising compounds were selected for further studies. Each of these agents exerted an antihypertensive effect upon oral administrations in conscious spontaneously hypertensive rats. At small doses, the new compounds appeared to be somewhat less potent than prazosin, but at the higher doses of 10-100 mumol/kg, two of them appeared to be even more efficacious antihypertensive agents than prazosin.

Animals↗
PubMed1982

Comparison of labetalol and clonidine in hypertension.

The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B(5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits until normotension was achieve, or intolerable side-effects occurred. The treatment with B and L or C was than continued in a cross-over fashion for two 6-week periods, with 3 week diuretic washouts and subsequent dose-titration periods between the treatment periods. At the end of B, the supine blood pressure (BP) was 156/101, and at the end of B + L and B + C it was 136/91 (p less than 0.001) and 137/91 (p less than 0.0001), respectively, pooling the data from both periods. At the end of B the standing BP was 155/115, and at the end of B + L and B + C 134/100 (p less than 0.001) and 139/106 (p less than 0.0001), respectively. The mean daily doses required were L 476 mg and C 0.335 mg. On a weight basis, labetalol had about 1/1400 of the potency of clonidine. 12 patients complained of tiredness and dry mouth on clonidine and 2 patients of unsteadiness on labetalol. Labetalol caused a psoriasiform rash on the hands in one patient and limb weakness in one patient.

Adult↗
PubMed1982

Peripheral hypotensive and central hypertensive effects of cimetidine.

Rapid intravenous (i.v.) injections of high doses (16-128 mumol/kg) of cimetidine induced a short-lasting (5-15 min) hypotension in anaesthetized rats. Diastolic pressure was reduced more than systolic pressure, suggesting vasodilatation. Heart rate was not affected. Diphenhydramine pretreatment (100 mumol/kg i.v.) did not antagonize the hypotensive effect of cimetidine. However, in the presence of diphenhydramine, cimetidine induced bradycardia. Intracerebroventricular administration of cimetidine or metiamide (2 mumol/rat) increased the blood pressure and heart rate. It is concluded that the hypotension after i.v. cimetidine is mediated by peripheral mechanisms. Since diphenhydramine pretreatment had no antagonistic effect cimetidine-induced hypotension could not be due to indirect H1-receptor stimulation caused by histamine liberation.

Animals↗