Influence of desoxycorticosterone on the reaction of isolated segments of coronary arteries to noradrenaline in the presence of pyrogallol

The effect of the desoxycorticosterone on the noradrenaline-induced relaxation of coronary arteries waw studied in vitro, after a known inhibitor of COMT, pyrogallol. Relaxation induced by noradrenaline was enhanced by desoxycorticosterone. Relaxation in response to noradrenaline was increased by desoxycorticosterone. Pyrogallol potentiated the responses of coronary strips to noradrenaline and also reduced or abolished the enhancing effects of desoxycorticosterone. It is concluded that desoxycorticosterone enhances the reponse of coronary smooth muscle to noradrenaline by inhibiting and enzymatic pathway for the inactivation of catecolamines.     

Influence of desoxycorticosterone on the response of calf coronary artery strips to adrenaline

The effect of desoxycorticosterone on the adrenaline-induced relaxation of coronary arteries was studied "in vitro". It resulted that the effect of adrenaline was enhanced by desoxycorticosterone. It is concluded that desoxycorticosterone potentiates the effects of adrenaline by inhibiting its inactivation by Catechol-O-methyltransferase.     

Response of isolated coronary artery strips to noradrenaline in the presence of desoxycorticosterone

The effect of desoxycorticosterone on the noradrenaline-induced relaxation of coronary arteries was studied "in vitro". It resulted that the effect of noradrenaline was enhanced by desoxycorticosterone. It is concluded that desoxycorticosterone potentiates the effects of noradrenaline by inhibiting its inactivation by Catechol-O-methyltransferase.     

Influence of dexamethasone on the responses of isolated coronary arteries to adrenaline

The effect of Dexamethasone on the adrenaline-induced relaxation was studied in vitro. Relaxation of response to adrenaline increased by Dexamethasone. We suggest that the Dexamethasone influence depends on inhibition of Catecol-O-methyl transferase (COMT).     

Influence of 6-methylprednisolone on responses of isolated coronary arteries to adrenaline

The effect of 6-Methylprednisolone on the adrenaline-induced relaxation was studied in vitro. Relaxation of response to adrenaline increased by 6-Methylprednisolone. We suggest that the 6-Methylprednisolone influence influence depends on inhibition of Catecol-O-methyl transferase (COMT).     

Effects of fetal urinary corticosteroids, catecholamines and kallikrein on PGE2 synthesis in monolayer cultures of human amnion and chorion cells

We have studied the effects of several compounds isolated from fetal urine on the production of PGE2 by amnion and chorion cells which were maintained in primary monolayer culture. We conclude that desoxycorticosterone and vanillylmandelic acid stimulate PGE2 synthesis by amnion, but adrenaline and kallikrein increase the biosynthesis of PGE2 by chorion. These data suggest that human fetal urine could play a major role in events of parturition.     

The role of immune factors in the coronary, chrono- and inotropic effects of adrenomimetics

The experiments on dogs under chloralose and urethan anesthesia have shown that intracoronary injection of anticardiac immune serum caused inversion of coronary vascular reaction to adrenaline and isoprenaline and elimination of cardiogenic depressor hemodynamic reflex, without decreasing adrenomimetic inotropic effect. The administration of immune complexes (horse serum antigens--specific rabbit antibodies) produced biphasic coronary vascular reaction to adrenaline and decreased by half reflex hypotension, without changing chrono- and inotropic adrenaline effects.     

Influence of pyridoxal-5'-phosphate on responses of isolated coronary arteries to noradrenaline, in the presence of pyrogallol

The effect of PLP on the noradrenaline-induced relaxation of coronary arteries was studied in vitro, after known inhibitor of COMT, Pyrogallol. Relaxation of response to noradrenaline were increased by PLP. Pyrogallol potentiated responses of coronary strips to noradrenaline and also reduced or abolished the enhancing effects of PLP. It is concluded that PLP enhances the response of coronary smooth muscle to noradrenaline by inhibiting a enzymatic pathway for the inactivation of catecolamines.     

Effects of triamcinolone and of desoxycorticosterone on renal function in sheep.

Sheep were treated for 10 or 17 days with triamcinolone acetonide, 0.1 mg/kg body weight/day, or desoxycorticosterone acetate, 0.1 mg/kg body weight/day, and the results of renal function studies during hydropenia and mannitol diuresis were compared with respective control periods. GFR was increased and urine concentration was unimpaired by treatment with triamcinolone. A consistent decrease in mannitol-induced Na excretion was observed, but with large variations in the mean change, in triamcinolone treatment periods. Treatment with desoxycorticosterone resulted in an increased GFR but with impaired urine concentrating capacity. The hypokalemia produced by desoxycorticosterone was not accompanied by an increase in urinary K excretion. During mannitol diuresis in sheep treated with desoxycorticosterone, there was a significant decrease in Na excretion when compared with control periods.     

Effect of mineralocorticoids on the Na, K-ATPase activity of the rat brain

The effect of desoxycorticosterone (DOC) on Na, K-ATPase activity was studied in vivo and in vitro on microsomal rat brain fractions. An hour after intramuscular administration of DOC a noticeable increase in the enzyme activity was observed. Preincubation of microsomal brain fractions with 5 and 15 mkg/ml of DOC caused a decrease in Na, K-ATPase activity, with the results evident 3-5 minutes after the addition of the hormone into the incubation medium. The idea of a two-phase hormonal effect is suggested. It is likely that desoxycorticosterone effect is realized both by the direct influence, on Na, K-ATPase of the brain plasma membrane and by the influence on the biosynthesis.     

Inhibitory effects of L-NG-nitro-arginine on the synthesis of EDRF and the cerebroarterial response to vasodilator nerve stimulation

Treatment with L-NG-nitro-arginine (L-NA) inhibited the brady-kinin-induced relaxation, mediated via EDRF, in dog coronary artery strips partially contracted with prostaglandin F2 alpha; the inhibition was prevented by L-, but not D-, arginine. Relaxation caused by nitroglycerin was not altered by L-NA. The release of EDRF, as assayed using dog coronary artery strips without endothelium, from perfused femoral artery segments with endothelium in response to acetylcholine and substance P was significantly reduced by treatment of the femoral artery with L-NA. The inhibitory effect was reversed by L-arginine. Relaxant responses of dog cerebral artery strips with and without endothelium to electrical stimulation of non-adrenergic, non-cholinergic nerves were suppressed by L-NA, whereas relaxation of coronary arteries with and without endothelium by the stimulation of adrenergic nerves was not influenced. The L-NA-induced inhibition was reversed by L-arginine. It is speculated that L-NA inhibits the synthesis of EDRF, as does L-NG-monomethyl arginine, and NO-like substance(s) produced plays an important role in transferring information from vasodilator nerves to smooth muscle in cerebral arteries.     

Heat production as a criterion of adrenergic regulation of metabolic processes of the myocardium

Bolus injection of adrenaline in coronary perfusion blood flow caused different-directed changes in coronary venous blood temperature. Directivity and myocardium heat production changes are determined by peculiarities of interactions between adrenergic and cholinergic mechanisms of cardiodynamics and myocardial metabolism regulation. Cholinergic blockade by atropine++ increases heat production and limits negative ino- and chronotropic components of cardiac adrenergic reactions. That increase is completely eliminated by subsequent obsidan blockade of beta-adrenoreceptors.     

Hypertension,Thrombosis, and Atherosclerosis in the Rat

A simple high fat diet containing cholic acid has been devised for producing hyperlipemia and an increased incidence of thrombosis in the small coronary vessels of the rat, but without producing significant atherosclerotic lesions. The influence on this syndrome induced by six weeks of desoxycorticosterone administration, 2 mg. daily, and 10 weeks of oral saline (1%) ingestion was investigated in 30 115-g. male rats. Marked hypertension developed only when it was induced prior to beginning the dietary feeding. In comparison to the control groups, the group that was both hyperlipemic and hypertensive had severer hypertension, severer hyperlipemia, double the mortality due to thrombosis and fatty streaks in the aorta but very few lesions of periarteritis nodosa. However, the early atherosclerotic lesions did not seem to be responsible for the increased production of thrombosis. It is therefore probable that under these experimental conditions hypertension has a more direct action on the production of thrombotic effect than that of worsening the atherosclerotic lesions.     

Ability of different hormones to substitute for progesterone in the induction of oestrous behaviour in oestrogen-treated overiectomized ewes

Behavioural responses to teaser males were recorded in oestrogen-treated ovariectomized ewes following 5 days pretreatment with various progestins, adrenal steroids or the oil vehicle. Hormones used were, progesterone, 5-dihydroprogesterone, corticosterone and desoxycorticosterone. No clear pattern emerged from records of soliciting behaviour, and only treatment with 5-dihydroprogesterone or desoxycorticosterone produced significantly greater receptivity quotients than injection of the oil vehicle. These results indicate that further studies with progesterone metabolites could increase understanding of the mechanisms controlling reproductive behaviour in the ewe.     

The effects of progestins,mineralocorticoids, glucocorticoids,and steroid solubility on the induction of sexual receptivity in rats

In the first experiment, progesterone and its 5α-reduced metabolite, 5α-dihydroprogesterone, dissolved in two different vehicles were compared for their effectiveness in facilitating lordosis behavior in ovariectomized estrogen-primed rats. When dissolved in oil vehicle, 5α-dihydroprogesterone was less effective than progesterone. However, when dissolved in Tween 80 solution, the two progestins were equally effective. In the second experiment, adrenal corticoids dissolved in Tween 80 solution were tested for their relative ability to facilitate sexual receptivity. Progesterone, desoxycorticosterone, and desoxycorticosterone acetate were equally effective in facilitating sexual receptivity. Aldosterone, corticosterone, and corticosterone acetate were no more effective than the vehicle in facilitating sexual receptivity.     

Cardiac Responses to Thermal,Physical, and Emotional Stress

We have studied the effect of a short period of exposure to the intense heat of a sauna bath on the electrocardiogram and plasma catecholamine, free fatty acid, and triglyceride concentrations in 17 subjects with apparently normal hearts and 18 persons with coronary heart disease. Similar observations were made on 11 of the 17 normal subjects and on 7 of the persons with coronary heart disease in response to exercise.Exposure to heat was associated with an increase in plasma adrenaline with no change in noradrenaline, free fatty acid, or triglyceride concentrations. Exercise was associated with the expected increase in both plasma noradrenaline and adrenaline concentrations. A heart rate up to 180 beats/min was observed in response to both heat and exercise. Apart from the ST-T changes inherent to sinus tachycardia, ST-T segment abnormalities were frequent in response to heat in both the subjects with normal and abnormal hearts, but little change occurred in the ST-T configuration when the subjects were exercised to produce comparable heart rates. Ectopic beats, sometimes numerous and multifocal, were observed in some subjects of both groups in response to heat, but not to exercise. It seems likely that the net unbalanced adrenaline component of the increased plasma catecholamine concentrations (which is also seen in certain emotional stress situations) is predominantly responsible for ischaemic-like manifestations of the electrocardiogram in susceptible subjects. The observations provide further validation for previously reported studies that it is the increased plasma noradrenaline in response to emotional stress that is associated with the release of free fatty acids and ultimate hypertriglyceridaemia, of probable importance in the aetiology of atheroma.     

Urinary excretion of free noradrenaline and adrenaline related to age, sex and hypertension in 265 individuals

Urinary excretion of free noradrenaline and adrenaline during 24 h in 265 individuals was determined and related to sex, age, and hypertension as one indicator of the average sympathetic drive. Noradrenaline was found to correlate positively with age in healthy individuals. Noradrenaline and adrenaline were lower in healthy women than in men during the first half of life expectancy. Catecholamine excretion was similar in men and women in the second half of life expectancy. In hypertensive individuals, catecholamine excretion was slightly higher in the first half, and significantly higher in the second half of life expectancy. We assume that the differences in catecholamine excretion can contribute to the sex-and age-related differences in incidence of cardiovascular diseases, such as hypertension and coronary heart disease.     

Urinary kallikrein in hypertensive animal models.

Urinary kallikrein excretion was studied in a number of animal models of hypertension. Kallikrein excretion was subnormal in spontaneously hypertensive rats as compared to Wistar/Kyoto rats and in rats made hypertensive by a clip on one renal artery. Kallikrein excretion was supranormal in rats made hypertensive by desoxycorticosterone and salt and in rats receiving desoxycorticosterone alone. It was subnormal after bilateral adrenalectomy. Kallikrein excretion increased in normotensive rats fed a low-sodium diet but was unchanged by a high-sodium diet. Thus, kallikrein excretion responded to changes in activity of sodium-retaining steroids and was not correlated with excretion of salt or water. In studies in dogs with stenosis of one renal artery kallikrein excretion was decreased on the stenoic side and the decrease correlated highly with the reduction in renal blood flow. While the role of the kallikrein-kinin system is still unclear the data indicate that the kidney may modify the initiation or maintenance of hypertension via this potent vasodilator system.     

The pulmonary hemodynamics changes under experimental myocardial ischemia in rabbits following increased arterial pressure

In acute experiments in anesthetized rabbits, changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the infusion of adrenaline and phenylephrine. The pulmonary artery pressure was increased following infusion of these drugs; however, it decreased to normal level in the condition of myocardial ischemia. Meanwhile the pulmonary vascular resistance was elevated to the same level in both cases. Following adrenaline infusion, the pulmonary artery blood flow and venous return increased and, in the condition of myocardial ischemia, they decreased to normal level, but the left atrial pressure was decreased. Following phenylephrine infusion, the pulmonary artery blood flow and venous return did not change and, in the condition of myocardial ischemia, these parameters decreased lower than normal level but the left atrial pressure was elevated. Thus we concluded that equal values of the pulmonary artery pressure in both cases were caused by changes of different character in the left atrial pressure. The differences of the changes character and values of the pulmonary artery flow under experimental myocardial ischemia following the infusion of adrenaline and phenylephrine were caused by different shifts of the venous return.     

The calibre of the Foramen of Panizza in Crocodylus porosus is variable and under adrenergic control

The foramen of Panizza is located within the outflow tract of the crocodilian heart, between the left and right aortas. It has been suggested that the foramen of Panizza has a variable calibre, which could explain the profound changes in the distribution of flows and pressure profiles recorded in the right and left aortas. We investigated this possibility using a modified in-situ perfused heart preparation in combination with isolated strip preparations from the outflow tract. In the perfused heart preparation, bolus injections of adrenaline increased the resistance in the foramen of Panizza, indicating a decrease in its diameter. Isolated strip preparations from the outflow tract showed a concentration-dependent increase in tension in response to adrenaline, while vasoactive intestinal polypeptide caused a relaxation in adrenaline pre-contracted strip preparations. We propose that an increase in the diameter of the foramen of Panizza may be important during pulmonary to systemic shunts to allow blood to flow from the left to right aorta (reverse foramen flow) in order to supply the carotid and coronary arteries. During non-shunting conditions, a constricted foramen may prevent excess flow from the right to left aorta during diastole.