PubMed Health⌕ Search

Biomedical subjects

J C van Meel

Publications and source records attributed to J C van Meel.

31 records · Page 2Linked to original sources
PubMed1982

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.

Adrenergic alpha-Agonists↗
PubMed1982

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. (b) The functional role of cardiac presynaptic alpha 2-adrenoceptors in the bradycardiac effect of clonidine and related congeners. In the pentobarbitone-anaesthetized rat, the stimulation of cardiac presynaptic alpha 2-adrenoceptors appears to be a highly relevant mechanism, which in combination with the facilitation of the vagal reflex bradycardia explains the bradycardiac action of clonidine and related drugs. (c) The possible extrasynaptic location of postsynaptic alpha 2- and beta 2-adrenoceptors in vascular smooth muscle. A comparison of the influence of the blocking potency of selective alpha 1- and alpha 2-adrenoceptor antagonists on the vasoconstrictor and tachycardia effects of catecholamines, either released endogenously or injected via an exogenous route, has suggested that the alpha 2- and beta 2-adrenoceptors are probably located at extrasynaptic sites, whereas the alpha 1-adrenoceptors are rather situated within the synapse. (d) The characterization of alpha-adrenoceptors involved in the central hypotensive and sedative activities of clonidine. Experiments with selective alpha-adrenoceptors blocking agents have revealed that the central alpha-adrenoceptors involved in the hypotensive and sedative effects of clonidine are most likely to correspond to the alpha 2-subtype.

Adrenergic alpha-Agonists↗
PubMed1982

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. A correlation study revealed that there exists a close correlation between the depressant influence of the calcium-antagonistic drugs on the vasoconstriction due to alpha 2-adrenoceptor stimulation and the calcium-antagonistic potency in vitro. Accordingly, it is speculated that the vasoconstriction due to alpha 2-receptor stimulation requires the influx of calcium ions from the extracellular space across the membrane. This process is obviously sensitive to the influence of calcium-antagonistic drugs.

Animals↗
PubMed1981

The effect of selective alpha 1- and alpha 2-adrenoceptor stimulation on intraocular pressure in the conscious rabbit.

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 was blocked by the selective alpha 2-adrenoceptor antagonist yohimbine. alpha 2-Agonists induced neither macroscopic ocular side effects, nor an effect on the pupil size. Possibly, the subclass of alpha 2-adrenoceptor stimulating drugs represents a group of new antiglaucomatous agents.

Adrenergic alpha-Agonists↗
PubMed1981

Characterization of alpha-adrenoceptor populations. Quantitative relationships between cardiovascular effects initiated at central and peripheral alpha-adrenoceptors.

The agonist selectivities of central (medullary) and peripheral (vascular) alpha-adrenoceptors were compared in order to investigate a possible similarity among these two alpha-adrenoceptor populations. Linear regression equations were derived between the alpha-adrenergic potencies, mediated by these two types of alpha-adrenoceptors for 21 structurally dissimilar alpha-adrenoceptor agonists. Hypotensive potency after intravenous administration to anesthetized, normotensive rats was determined as a measure of central alpha-adrenergic activity and expressed as pC25, obtained from log dose-response curves. Peripheral alpha-adrenergic potency was quantified by means of the hypertensive effect elicited in pithed, normotensive rats after intravenous injections, yielding pC60 as the biological variable. A most significant linear relationship was generated between central hypotensive activity (pC25) and peripheral hypertensive potency (pC60), provided that log P' (octanol/buffer; pH 7.4, 37 degrees C) was included into the regression in a parabolic form. This result indicates that the central (medullary) alpha-adrenoceptors and the peripheral (vascular) alpha-adrenoceptor sites, which are excited by the drugs in question, make identical demands upon their agonists. The difference in accessibility to these peripheral and central alpha-adrenoceptor populations is adequately accounted for by a parabolic description in log P'. The apparent contradiction of this finding with the suggestion that central, hypotensive alpha-adrenoceptors are of the alpha 2 type and peripheral, vascular alpha-adrenoceptors belong to the alpha 1 subpopulation is discussed. The recent identification of an additional subclass of postsynaptic, vascular alpha 2-adrenoceptors and the lack of pronounced differential stimulating activity of the agonists at peripheral alpha-adrenoceptors may explain the present findings and clarify the paradox.

Animals↗
PubMedDate not supplied

Influence of nifedipine on functional responses in vivo initiated at alpha 2-adrenoceptors.

The pressor effects of intravenous B-HT 920 in pithed cats were sensitive to antagonism by yohimbine (1 mg/kg i.v.), but not by prazosin (1 mg/kg i.v.). In contrast, prazosin profoundly affected the vasoconstriction caused by intravenous (-)-phenylephrine, whereas yohimbine only slightly influenced this response. These results confirm and extend earlier observations which favor a distinct subclassification of vascular postsynaptic alpha-adrenoceptors into alpha 1- and alpha 2-subtypes. Vasoconstriction in pithed cats by B-HT 920 was markedly antagonized by low doses (30 and 100 micrograms/kg) of nifedipine in a noncompetitive manner. The hypertensive responses to (-)-phenylephrine were moderately attenuated in a competitive fashion. These findings are consistent with the concept that extracellular calcium ions are indispensable for linking vascular alpha 2-adrenoceptor activation to vasoconstriction in vivo. Nifedipine (up to 1 mg/kg i.v.) neither interfered with the tachycardia induced by electrical stimulation in pithed normotensive rats nor influenced the inhibitory effect of B-HT 920. Clonidine's (0.3 mg/kg i.p.) prolongation of the hexobarbitone-induced loss of the righting reflex in mice was unchanged after nifedipine administration (up to 1 mg/kg i.p.). The central hypotensive action of clonidine in anesthetized cats (1 microgram/kg via vertebral artery) and in anesthetized normotensive rats (3-30 micrograms/kg i.c.v.) was reduced by nifedipine (30 and 100 micrograms/kg i.v. or i.c.v.). The results show a differential influence of nifedipine on functional responses in vivo caused by stimulation of pre- and postsynaptic alpha 2-adrenoceptors. In contrast to its inability to inhibit alpha 2-adrenoceptor-mediated effects at presynaptic sites, this calcium entry blocker impairs postsynaptic alpha 2-adrenoceptor-induced responses.

Animals↗
PubMedDate not supplied

alpha 1- and alpha 2-adrenoceptor stimulation in the isolated perfused hindquarters of the rat: an in vitro model.

In the isolated perfused hindquarters of rats pretreated with reserpine, vasoconstrictor responses were induced by activation of postjunctional alpha 1- and alpha 2-adrenoceptors. B-HT 920 and methoxamine were used as selective stimulants of alpha 2- and alpha 1-adrenoceptors, respectively. Prazosin (pA2 8.83) exhibited a competitive antagonism toward methoxamine-induced vasoconstrictor responses, whereas yohimbine (pA2 8.95) effectively antagonized B-HT 920-induced vasoconstriction in a competitive manner. When calcium was omitted from the perfusion fluid, no vasoconstriction via alpha 2-adrenoceptors could be evoked. On the other hand, raising the extracellular calcium concentration in the perfusion fluid enhanced the alpha 2-adrenoceptor-mediated vasoconstrictor effects. Vasoconstriction via postjunctional alpha 1-adrenoceptors seemed hardly, if at all, dependent on extracellular calcium. The calcium entry blockers Co2+, La3+, and nisoldipine selectively inhibited the alpha 2-adrenoceptor-induced vasoconstriction in a noncompetitive manner. The results further support the concept that extracellular calcium is a prerequisite for the process of vasoconstriction induced by activation of postjunctional alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Pharmacology of calcium entry blockers: interaction with vascular alpha-adrenoceptors.

The pharmacology of calcium entry blockers (CEB), as used in various types of cardiovascular disease, is reviewed. Their vasodilator potency is analyzed, which is the most common therapeutic characteristic of all CEB, apart from the antiarrhythmic activity of verapamil. All CEB relax vascular smooth muscle, particularly in arteriolar beds, thus reducing peripheral vascular resistance. Arteriolar relaxation appears to be associated with inhibition of transmembrane calcium influx. Recent studies have demonstrated that vasoconstriction induced by stimulation of vascular postsynaptic alpha 2-adrenoceptors, using selective agonists, is reduced by CEB through a noncompetitive mechanism. However, vasoconstriction evoked by selective excitation of vascular alpha 1-adrenoceptors remains virtually uninfluenced by CEB. The selective interference of CEB with alpha 2-adrenoceptor stimulation suggests that calcium movement is associated with alpha 2-adrenoceptor stimulation. This mechanism may further contribute to the vasodilator effect of CEB by inhibiting that part of vascular tone evoked by the stimulation of alpha 2-adrenoceptors by endogenous catecholamines.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

[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. This interference, which can be demonstrated in various animal species, implicates that the pressor effect of an alpha 2-adrenoceptor agonist is diminished by the CA and by N alpha 2-EDTA. However, the vasoconstriction initiated by alpha 1-adrenoceptor agonists is hardly reduced by CA. Accordingly, the interaction is selective for alpha 2-adrenoceptors. 3. The following hypothesis is submitted: After formation of the alpha 2-adrenoceptor/agonist complex there occurs a transmembranous influx of extracellular calcium ions. This influx, which is inhibited by CA, is probably indispensable for the activation of contractile proteins. 4. Accordingly, the vasodilator activity of the CA might be explained as follows: the CA inhibit the alpha 2-receptor mediated component of the vasoconstriction, induced by endogenous catecholamines, without influencing the alpha 1-receptor component of the pressor effect.

Animals↗