[Interaction between calcium antagonists and vascular postsynaptic alpha-receptors].

1. The present review deals with the vascular action of calcium antagonists (CA) at the cellular level, emphasizing the interference between CA and postsynaptic alpha 2-adrenoceptors in the resistance vessels. 2.

Guanfacine and clonidine: antihypertensive and withdrawal characteristics after continuous infusion and its interruption in the spontaneously hypertensive and normotensive rat.

In conscious unrestrained spontaneously hypertensive and normotensive rats, prepared with permanently indwelling abdominal aortic catheters, the effects of blood pressure and heart rate of a 12-day continuous subcutaneous infusion of guanfacine (10 mg/kg/day) and clonidine (500 micrograms/kg/day) and sudden interruption of these treatments were studied. Both drugs significantly and consistently reduced the mean arterial pressure and heart rate throughout the infusion period in the SH rats, but not in the normotensive animals. The magnitude of the effects of both drugs in the SH rat were similar.

Binding characteristics of [3H]guanfacine to rat brain alpha-adrenoceptors. Comparison with [3H]clonidine.

The tritium-labeled alpha-adrenoceptor agonist and antihypertensive drug guanfacine, N-amidino-2-(2,6-dichlorophenyl)-acetamide (sp. act. 24.

Impairment by nifedipine of vasopressor responses to stimulation of postsynaptic alpha 2-adrenoreceptors in ganglion--blocked rabbits. Further evidence for the selective inhibition of postsynaptic alpha 2-adrenoreceptor-induced pressor responses by calcium antagonists.

1 After ganglionic blockade and bilateral vagotomy, vasopressor responses induced by activation of postsynaptic alpha 1- and alpha 2-adrenoreceptors were elicited in the intact circulatory system of rabbits. 2 The hypertensive effects of the selective stimulating agents methoxamine (alpha 1-agonist) and B-HT 920 (alpha 2-agonist) were effectively antagonized by the adrenoreceptor antagonists prazosin and yohimbine, respectively. These findings confirm the existence of two types of postsynaptic alpha-adrenoreceptors (alpha 1- and alpha 2-type) in vascular smooth muscle of rabbits.

Involvement of alpha 1- and alpha 2-adrenoceptors in the vasoconstriction caused by ergometrine.

In pithed normotensive rats, the pressor effects evoked by i.v. serotonin (5-HT) and ergometrine were analysed using the relatively selective alpha 1-, alpha 2- and serotonin antagonists prazosin, yohimbine methysergide, respectively.

Inhibition of R 28935- and R 29814-induced hypotension by prazosin in anaesthetized normotensive rats.

The intravenous administration of erythro 1-(1-[2-(1,4-benzodioxane-2-yl)-2-hydroxyethyl]-4-piperidyl)-2-benzimidazolinone R 28935) and the threo from R 29814 to anaesthetized normotensive rats showed a dose-dependent decrease in mean arterial pressure. Previous (-1 hr) intraperitoneal (0.1 mg/kg) as well as subcutaneous (0.

Hypotensive properties of benzodioxane derivatives structurally related to R 28935. Comparison of activity with some receptor affinities.

Hypotensive activities were determined of some derivatives of erythro 1-(1-[2-(1,4-benzodioxane-2-yl)-2-hydroxyethyl]-4-piperidyl)-2-benzimidazolinone (R 28935) following intravenous administration to anaesthetized normotensive rats. Introduction of chlorine into the benzimidazolinone part of R 28935 negatively influenced the hypotensive potency as did opening of the dioxane ring. An appropriate substituent restored the hypotensive effectiveness of the "opened" structures.

Differential effects of selective alpha 1- and alpha 2-adrenoceptor agonists on intraocular pressure in the conscious rabbit.

In the present study the influence of topically applied selective alpha 1- and alpha 2-adrenoceptor agonists on intraocular pressure and the diameter of the pupil was investigated in conscious rabbits. Selective stimulation of the alpha 1-subtype of receptors induced an elevation in intraocular pressure, accompanied by mydriasis, whereas stimulation of the alpha 2-subtype caused a marked and dose-dependent ocular hypotensive response, which could be blocked by the selective alpha 2-adrenoceptor antagonist yohimbine. After application of the non-selective alpha-adrenoceptor agonist clonidine the alpha 2-adrenoceptor mediated decrease in IOP is probably counteracted by a pressor effect due to the stimulation of alpha 1-adrenoceptors.

Calcium antagonists and alpha 2-adrenoceptors: possible role of extracellular calcium ions in alpha 2-adrenoceptor-mediated vasoconstriction.

A survey concerning the influence of calcium antagonists on the vasoconstriction induced by the selective stimulation of either postsynaptic alpha 1- or alpha 2-adrenoceptors in the resistance vessels of pithed rats and cats, as well as in ganglion-blocked rabbits, is presented. In every species studied, all calcium antagonists (organic: verapamil, D 600, diltiazem, nifedipine, nisoldipine, and a variety of new compounds; inorganic: Co2+, Ni2+, and Mn2+) significantly reduced the pressor response towards the stimulation of postsynaptic vascular alpha 2-adrenoceptors with B-HT 920 (and other agonists). However, the various calcium antagonists showed little influence on the vasoconstriction provoked by the excitation of vascular postsynaptic alpha 1-adrenoceptors.

Central and peripheral alpha-adrenoceptors.

The recent interest in the characterization and functional, role of alpha-adrenoceptors has prompted us to study the following different, although interdigitated, lines of research: (a) The functional role of calcium ions in the process of vasoconstriction, induced by alpha 2-adrenoceptor stimulation. We have shown in various animal species that the vasoconstriction induced by alpha 2-adrenoceptor stimulation with specific agonists is impaired by various organic and inorganic calcium antagonists. This finding suggests that the influx of extracellular calcium is required in order to enable the occurrence of vasoconstriction, mediated by the stimulation of vascular alpha 2-adrenoceptors.

Vascular aspects of calcium antagonists.

Calcium antagonistic drugs have been recognized as useful antiarrhythmic agents for approximately a decade. More recently, however, their vascular effects have been shown to be of potential therapeutic and pharmacological interest, especially in the treatment of angina pectoris involving coronary arterial spasm and possibly also of hypertension. The present survey is dealing with the circulatory changes of the calcium antagonists, describing the influence of the drugs on the systemic and coronary circulation, as well as on special vascular beds like the renal and cerebral circulatory tracts.

A comparison of peripheral pre- and postsynaptic alpha 2-adrenoreceptors using meta-substituted imidazolidines.

1 The cardiac presynaptic activity, as derived from the inhibition of tachycardia to electrical stimulation of the cardiac sympathetic nerve in pithed, normotensive rats of 8 meta-substituted phenyl(imino)imidazolidines (2, 3- and 2,5- derivation) was determined. 2 The agonistic activity of the imidazolidines was measured with respect to vascular alpha 1- and alpha 2-adrenoreceptors. Accordingly, the increase in diastolic pressure of pithed, normotensive rats to intravenous administration of the imidazolidines was evaluated after pretreatment with 5% w/v glucose solution, yohimbine (1 mg/kg), prazosin (0.

Serum and urine concentrations of 5-methoxypsoralen after oral administration.

Serum and urine concentrations were measured after oral administration of 5-methoxypsoralen (0.6 mg/kg or I.2 mg/kg) to psoriasis patients.