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Blood pressure response to bolus administration of vasoactive drugs in the rat.

The time course of systemic blood pressure response in normotensive anaesthetized rats was studied after a bolus administration of standard doses (0.4 microgram/kg) of noradrenaline, adrenaline, isoprenaline, acetylcholine, serotonin, bradykinin, and histamine. The single stimulus of a vasoactive agent elicits a blood pressure deviation with typical phasing. The time dimension of the individual wave is less variable and less dose dependent than their amplitude. Under the given experimental conditions the blood pressure response is predominantly determined by the peripheral vasomotor reactions; the cardiac component is of minor importance. Though the overall responses to the individual drugs are quite characteristic, they seem to comprise several common components. Thus the peripheral vascular system is supposed to consist of different regulatory subsystems which take part in the systemic blood pressure control by typically timed responses. The pattern of the reaction is then given by their unequal combination and various intensity.

Animals↗

Impaired skeletal muscle vasomotor response to infused noradrenaline in baboons with obstructive jaundice.

1. We have measured muscle blood flow by a 133Xe clearance technique, and its response to noradrenaline in baboons before and 2 weeks after ligation of the bile ducts when they were jaundiced. 2. In the normal baboons, the response to noradrenaline was a dose-dependent decrease in muscle blood flow. 3. Bile-duct ligation caused no significant alteration in skeletal muscle blood flow but the response to noradrenaline in the jaundiced baboons was significantly attenuated. This effect was not observed in four sham-operated baboons.

Animals↗

[Effect of pharmacological substances on nociceptive vasomotor reflexes in experiments on unanesthetized animals].

Experiments on unanesthetized cats (conscious and curarized) were made to analyze the method of studying the effect of pharmacological substances on the pressor vasomotor reflexes produced by nociceptive stimulation. It was shown that the activity profiles of the drugs depend not only on their cardiovascular properties but also on the parameters of stimulation applied to the reflex recording, which is related to the shape of the curve of reflex magnitude dependence on the stimulation intensity. The most precise test in the application of the method to the unanesthetized animals involved the recording of the threshold of reflex occurrence, with the use of curare-like drugs being mandatory. Making of experiments without use of the curare-like agents or without considering the shape of the curve of reflex magnitude dependence on the parameters of stimulation might lead to errors in the appraisal of the results obtained.

Anesthesia↗

Hormone replacement therapy and symptom reporting in menopausal women: a population-based study of 35-65-year-old women in mid-Sweden.

OBJECTIVE: To measure the prevalence rate of hormone replacement therapy (HRT) in the general population and to see whether HRT users report less symptoms, better general health and less use of other palliative than non-users and previous users. METHODS: The study was performed in 1995 as a cross-sectional postal questionnaire study in seven counties in mid-Sweden. The questionnaire was sent to a random sample of 4200 35-64-year-old women of whom 2991 responded. The age distribution of responders and non-responders was similar 49.6+/-8.5 and 49.8+/-8.7 years, respectively. The main outcome measures were vasomotor and general symptoms in relation to menstrual status and HRT. RESULTS: Fifteen percent were on HRT and 2.3% had stopped treatment during the past year. Thirteen percent used other palliatives. Twenty-five percent of premenopausal women experienced any vasomotor symptoms, as compared with 51% of menopausal and 40% of postmenopausal women. Those on HRT reported higher frequencies than non-users of all symptoms except for sweating during the daytime. In addition, menopausal women experienced more of other symptoms, usually not associated with the menopause, than premenopausal and postmenopausal women. HRT users reported a significantly worse perceived health and they took other palliatives drugs to a larger extent than HRT non-users. CONCLUSION: HRT seemed to be effective in relieving some vasomotor symptoms but did not affect the prevalence of other symptoms or perceived health, in spite of the fact that women on HRT supplemented their therapy with palliative drugs to a larger extent than other women.

Adult↗

Effect of the drug AS2 on the central and peripheral mechanisms of vascular tone regulation.

The effect of the compound AS2 (N'-benzhydryl, N''-allylpiperazine dihydrochloride) on the central and peripheral mechanisms of vascular tone regulation is studied. Six series of experiments on cats are carried out. The effect of the compound is tested on a model of central-hypertensive reaction, on the spontaneous bioelectrical activity of the renal nerve, on the transmission of excitation to the upper cervical ganglion and the ganglia of the solar plexus. Experiments are made to study its adrenolytic a-d myotropic properties. Cinnarizine is tested as control. The results show that the compound AS2, similar to Cinnarizine, affects the central and peripheral mechanisms of vascular tone regulation. In small doses (1-5 mg/kg) AS2 manifests poor myotropic properties. Administration of the drug in doses of 10-20 mg/kg results in considerable inhibition of the vasomotor centres, brief disturbances in the excitation transmission in the sympathetic ganglia and slight inhibition of adrenergic transmission.

Animals↗

Dipyridamole, an underestimated vascular protective drug.

Dipyridamole, developed almost half a century ago, acts by inhibiting nucleoside transport, which increases adenosine levels leading to inhibition of platelet aggregation and vasodilatation mainly in the coronary tree. It is a vaso-protective drug with proven efficacy in the prevention of strokes. Adenosine receptor 2 inhibitory purines, ubiquitously available in food and drink, inhibit the vasomotor effects of dipyridamole but not its action on platelet aggregation. This and the slow build-up of blood levels of dipyridamole after oral application may explain why incidents of drug-induced angina ("coronary steal") were never reported in the prevention trials. The prevention of arterial thrombosis and the positive remodeling of the arterial system (arteriogenesis) by elevated blood flows suggest that dipyridamole may be able to halt the progression of organ manifestations of atherosclerosis. Clinical trials for the secondary prevention of vascular occlusions in other vascular beds should be encouraged.

Adenosine↗

Vascular dopamine receptors in the canine hindlimb.

1 Increases in femoral blood flow were produced by intra-arterial injections of dopamine (5-50 mug) in some but not all anaesthetized dogs studied, following treatment with the alpha-adrenoceptor antagonist, phentolamine. 2 The dilator effect of dopamine was not due to inhibition of adrenergic vasomotor tone as it was not affected by pharmacological procedures which completely abolished the activity of vastomotor nerves. 3 Blockade of vascular beta-adrenoceptors using propanolol reduced the flow increases produced by dopamine much less than it did those produced by isoprenaline. 4 Responses to dopamine were significantly depressed by intra-arterial administration of ergometrine (0.5 mg). This dose of ergometrine did not reduce femoral dilator responses to acetylcholine, histamine, isopienaline, bradykinin, or 5-hydroxytryptamine. 5 It is concluded that the femoral vascular bed in the dog contains specific vasodilator receptors for dopamine. Ergometrine appears to be a selective antagonist of dopamine at these receptors.

Acetylcholine↗

[The effect of calcium channel blockers on activity in the sympathetic nerves, on the vasomotor reflex and on cerebral circulation].

Experiments on cats showed that calcium canal blockers of the dihydropyridine series (nimodipine, nifedipine) and, to a lesser measure diphenylpiperazine derivatives increase the activity in sympathetic nerves attributable to the central effect of the drugs. Cinnarizine had a diametrically opposite effect. Cinnarizine, nimodipine, and nifedipine reduced the reflex pressor response of the arterial pressure, whereas flunarizine mainly promoted the vasomotor reflex. Therefore, the central stimulating effect of flunarizine dominated over its peripheral vasodilative action. Nifedipine caused the most pronounced increase in cerebral blood flow, followed by nimodipine, flunarizin, and cinnarizine.

Animals↗

Pharmacological investigation on the neurohumoral transmission of the vasomotor regulation.

Renal efferent sympathetic activity and its changes due to stimulation of the central stump of the vagal, sciatic and ulnar nerves were investigated. In addition, the effect on basal activity and sympathetic reflexes of drugs with well defined site of action was studied (diazepam, tofizopam, phentolamine, dihydroergotamine, chlorpromazine, reserpine, clonidine, atropine, methysergide and phenindamine). The sympathetic efferent activity and the changes in sympathetic reflexes allowed conclusions to be drawn as to the functional state of the vasomotor centre. Neither methysergide nor phenindamine inhibited efferent sympathetic activity or influenced sympathetic reflexes. These findings exclude the possibility of serotonin or histamine being the transmitter substance in the vasomotor neurone. Experiments with atropine revealed that the muscarinic action of acetylcholine does not figure in the sympathetic inhibitory or excitatory reflex processes. Of the drugs investigated only diazepam and clonidine inhibited efferent sympathetic activity. Clonidine was more selective and acted in much lower doses (20 micrograms/kg) than diazepam (0.5--1 mg/kg). The alpha blocking agents inhibited the viscero-sympathetic inhibitory reflex arch more intensely than the somato-sympathetic inhibitory one. The transmitter is presumably noradrenaline. The sympathetic excitatory reflexes were decreased by diazepam and tofizopam and increased by clonidine and phentolamine. The other substances were ineffective. As to the transmitter substance figuring in the sympathetic excitatory reflexes no unequivocal answer could be obtained in the present experiments.

Animals↗

Clinical pharmacology of ACE inhibition.

The radioimmunological determinations of immunoreactive 'angiotensin II' do not truly reflect angiotensin-(1-8)octapeptide levels, and thus cannot provide an accurate reflection of the efficacy of angiotensin-converting enzyme (ACE) inhibition. Elaborate methods are necessary to measure specifically the octapeptide angiotensin II. This methodology confirms that ACE inhibitors reduce circulating angiotensin II and that tolerance to the angiotensin II-lowering effect of ACE inhibitors does not develop, even after prolonged administration. Furthermore, a marked reduction of angiotensin II levels can be shown even in patients with primary aldosteronism. At peak blockade of ACE, the level of plasma angiotensin II is still related to circulating active renin and angiotensin I. The possible independent role of tissue renin-angiotensin systems in determining vasomotor tone is an interesting hypothesis. However, any discussion of whether tissue or plasma renin determines the pharmacologic effect of ACE inhibitors should be based on the simultaneous measurement of angiotensin-(1-8)octapeptide under steady-state conditions in tissue and plasma.

Angiotensin-Converting Enzyme Inhibitors↗

[Reflex sympathetic algodystrophy--the therapeutic options].

The patients entering this study were divided into 3 series according to the administered drug treatment, being then followed up for at least 28 days for the main symptoms (pain, tumefaction, vasomotor disturbances, limited movements). The more satisfactory results were obtained in the patients receiving prednisone, indomethacin, propranolol, sympatholytics, vasodilators, calcium anabolisants, tranquilizers to which, at the right time, massage and kinesitherapy were associated.

Adult↗

Treatment of menopausal vasomotor symptoms.

The Women's Health Initiative finding that taking estrogen plus a progestin for more than five years increased the risk of cardiovascular disease and breast cancer left the safety of using estrogen to treat hot flashes open to question. How low a dose and how short a duration would be safe and effective are unknown. Lifestyle changes, antidepressants, alpha-2 agonists, anticonvulsants, phytoestrogens and other dietary supplements have been tried as alternatives to estrogen, with mixed results.

Cimicifuga↗

[Effect of imipramine on the vasomotor tone, blood supply and activity of the heart].

In tests conducted on anesthetized cats it was shown that imipramine used in doses of 1 and 3 mg/kg causes hypertension, increases the vascular tone in the kidneys and limbs. In doses of 5 and 10 mg/kg the drug provokes a short-lived (1--3 minutes) hypertension with a subsequent prolonged drop of the arterial pressure. The tonicity of the kidney and limb arteries changes in the same way as the arterial pressure, but the vascular tone in the heart only falls. In these doses imipramine blocks the adrenergic transmission of the excitation from the sympathetic nerve to the effector, e. g. produces a sympatholytic effect. Imipramine in a dose of 1 mg/kg intensifies the coronary circulation and then the oxygen absorption by the heart increases to a still greater degree. This is attended by the development of tachycardia, a greater cardiac output and an intensified contractility of the myocardium. In doses of 5 and 10 mg/kg imipramine protractedly reduces the cardiac ejection, coronary blood flow and significantly lowers the contractile function of the heart muscle.

Animals↗