Biomedical subjects

B Wilffert

Publications and source records attributed to B Wilffert.

100 records · Page 6Linked to original sources

PubMed1981

Vascular smooth muscle contraction initiated by postsynaptic alpha 2-adrenoceptor activation is induced by an influx of extracellular calcium.

Vasoconstriction in pithed, normotensive rats elicited via stimulation of postsynaptic alpha 2-adrenoceptors by B-HT 920 was antagonized by EDTA and the calcium antagonists nifedipine, D 600 and verapamil, whereas pressor responses to the alpha 1-agonist methoxamine were unaffected. This indicates that vasoconstriction in vivo initiated via postsynaptic alpha 2-adrenoceptors requires an influx of extracellular calcium. Thus, the antihypertensive effect of calcium antagonists may be based upon a diminution of vascular tone maintained by postsynaptic alpha 2-adrenoceptors.

Animals↗

PubMed1981

Organic and inorganic calcium antagonists reduce vasoconstriction in vivo mediated by postsynaptic alpha 2-adrenoceptors.

The influence of various calcium antagonists and divalent metal cations on the pressor responses induced by the selective alpha 1-adrenoceptor agonist methoxamine and the selective alpha 2-adrenoceptor stimulating agent B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]-azepine) was studied in pithed rats. 1. The calcium antagonists verapamil, D 600 and nifedipine, when given intraarterially (i.a.) in doses up to 1 mg/kg did not influence the pressor effects of methoxamine. Only higher amounts of these calcium antagonistic drugs (1 - 3 mg/kg i.a.) somewhat reduced this pressor response. 2. The vasoconstriction due to B-HT 920, as reflected by the increase in diastolic pressure, was markedly inhibited by verapamil, D 600 and nifedipine in a dose-dependent manner. In low doses a parallel displacement to the right was observed, whereas in higher amounts the shift was non-parallel. 3. The divalent cations MN2+, Ni2+ and Co2+ (0.05 - 0.15 mmol/kg i.a.) hardly affected the pressor effect of methoxamine, whereas B-HT 920-induced vasoconstriction was highly sensitive to these metal ions. La3+ and Mg2+ were ineffective. 4. The calcium antagonists verapamil, D 600 and nifedipine displayed only minor affinities for [3H]prazosin (alpha 1) as well as [3H]clonidine (alpha 2) binding sites of rat brain membranes. 5. It is concluded that an influx of extracellular Ca2+ is necessary for the vasoconstriction in vivo initiated by stimulation of vascular postsynaptic alpha 2-adrenoceptors. On the other hand, vasopressor responses to alpha 1-adrenoceptor stimulation are not directly dependent on a transmembrane influx of calcium ions.

Adrenergic alpha-Agonists↗

PubMed1981

Muscarinic effects of various isoarecaidine esters in sympathetic ganglia.

1 The pressor effects of various tertiary and quaternary isoarecaidine esters in both pithed and anaesthetized rats are reported. In order to elucidate the mechanism of action, various experiments were carried out with the quaternary isoarecaidine methyl ester (Q-4-Me). 2 Treatment with mecamylamine, dexetimide, reserpine and phentolamine abolished or reduced the pressor response to Q-4-Me, whereas pretreatment with cocaine gave rise to a prolonged pressor effect. Plasma noradrenaline levels were significantly increased after the infusion of Q-4-Me. 3 From the results it can be concluded that the pressor effects brought about by the quaternary compounds can be attributed to stimulation of nicotinic and muscarinic receptors in sympathetic ganglia. The consequences of interaction with muscarinic receptors predominate over the effects due to minimal interference with nicotinic receptors by the drug.

Anesthesia↗

PubMedDate not supplied

Protective activity of nifedipine and R 58735 upon damage caused by global ischemia in the guinea pig heart-lung preparation.

In the guinea pig heart-lung preparation, the protective effects of nifedipine and R 58735 on cardiovascular alterations following mild (35 min) and severe (60 min) ischemia and reperfusion (30 min) were studied. Nifedipine and R 58735 were equi-protective against the effects of mild ischemia with respect to functional (LVP, dp/dt, and cardiac output) and biochemical (ATP, CrP, and adenylate charge) parameters. A clear difference, however, was observed between nifedipine and R 58735 upon severe ischemia, where R 58735 produced a significantly greater protection of functional, but not of biochemical parameters. Since no significant differences between the two compounds were found with respect to the concentrations of high energy phosphates after 35 and 60 min of ischemia before reperfusion, an energy sparing effect is not likely to be responsible for the difference between nifedipine and R 58735 in severe ischemia. An additional protective effect of R 58735 upon reperfusion in severe ischemia experiments may explain the difference between the two compounds.

Adenosine Triphosphate↗

PubMedDate not supplied

Interaction between beta 2-adrenoceptor-mediated vasodilation and alpha 2-adrenoceptor-mediated vasoconstriction in the pithed normotensive rat.

With pithed normotensive rats we studied the interaction between beta 2-adrenoceptor-mediated vasodilation and pressor responses elicited by vasopressin, the selective alpha 2-adrenoceptor agonists B-HT 920 and UK 14,304, and the alpha 2-adrenoceptor-mediated pressor responses of (--)-norepinephrine, tyramine [via neuronally released (--)-norepinephrine], alpha-methylnorepinephrine, and (--)-epinephrine. Salbutamol was used as a selective agonist of beta 2-adrenoceptors. The selective beta 2-adrenoceptor antagonist ICI 118,551 was employed to reveal the intrinsic beta 2-adrenoceptor activation induced by alpha-methylnorepinephrine and (--)-epinephrine, measured as a potentiation of the increase in diastolic pressure. Two types of interaction between beta 2-adrenoceptor-mediated vasodilation and alpha 2-adrenoceptor-mediated vasoconstriction were found. The effect of the alpha 2-adrenoceptor agonists was attenuated in most cases. However, intravenously administered (--)-norepinephrine elicited an alpha 2-adrenoceptor-mediated vasoconstriction not attenuated by beta 2-adrenoceptor-mediated vasodilation. These results are interpreted as indications for two different populations of vascular alpha 2-adrenoceptors. Neuronally released (--)-norepinephrine activated alpha 2-adrenoceptors, and its effect was attenuated by beta 2-adrenoceptor-mediated vasodilation in contrast to that of intravenously administered (--)-norepinephrine. Therefore, an intrasynaptic and extrasynaptic population of vascular alpha 2-adrenoceptors as postulated. In contrast to (--)-norepinephrine, intravenously administered (--)-epinephrine seems to activate predominantly intrasynaptic alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Interaction between beta 2-adrenoceptor-mediated vasodilation and alpha 1-adrenoceptor-mediated vasoconstriction in the pithed normotensive rat.

With pithed normotensive rats we studied the interaction between beta 2-adrenoceptor-mediated vasodilation and alpha 1-adrenoceptor-mediated vasoconstriction. The selective beta 2-adrenoceptor agonist salbutamol was used to elicit vasodilatation. To induce alpha 1-adrenoceptor-mediated vasoconstriction, the selective alpha 1-adrenoceptor agonists cirazoline, St 587, and methoxamine were used. Furthermore, the alpha 1-adrenoceptor-mediated vasopressor effects of intravenously administered (--)-norepinephrine, and (--)-norepinephrine released from neurons by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazine iodide (DMPP), the muscarinic ganglionic stimulant McN-A-343, electrical stimulation of the spinal cord, and the indirect sympathomimetic agent tyramine, were studied. By using the selective beta 2-adrenoceptor antagonist ICI 118,551, the interaction between the alpha 1-adrenoceptor-mediated vasoconstriction of (--)-epinephrine and alpha-methylnorepinephrine with their intrinsic beta 2-adrenoceptor agonistic effects was investigated. Two types of interaction between alpha 1-and beta 2-adrenoceptor-mediated vascular effects were found. Cirazoline and McN-A-343 activated alpha 1-adrenoceptors, inducing a vasoconstriction not affected by beta 2-adrenoceptor-mediated vasodilation. However, methoxamine at low doses, St 487, DMPP, electrical stimulation, intravenously administered (--)-norepinephrine, (--)-epinephrine, and alpha-methylnorepinephrine activated alpha 1-adrenoceptors, and their effect was attenuated by vasodilation. At low doses, tyramine stimulated alpha 1-adrenoceptors that were not sensitive to beta 2-adrenoceptor-mediated vasodilation, in contrast to the population of alpha 1-adrenoceptors activated at high doses of tyramine. It is hypothesized that there exist two different populations of alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Influence of Bay k 8644 on pressor effects of B-HT 920 and cirazoline in pithed cats.

We studied interactions between the putative calcium entry promotor Bay k 8644 and alpha 1-adrenoceptor-mediated increases in diastolic pressure elicited by cirazoline as well as alpha 2-adrenoceptor-mediated pressor responses induced by B-HT 920 in pithed cats. Bay k 8644 (0.01-1 mg/kg, i.a.) did not affect the log dose-pressor response curve of cirazoline, but slightly potentiated the increase in diastolic pressure elicited by B-HT 920. After attenuation of the B-HT 920-induced pressor effects by the calcium entry blocker nifedipine (0.1 mg/kg, i.a.), Bay k 8644 (0.1 mg/kg, i.a.) strongly enhanced the pressor response. The increase in diastolic pressure elicited by cirazoline was not affected by nifedipine (0.1 mg/kg, i.a.), and the addition of Bay k 8644 (0.1 mg/kg, i.a.) had no effect. We conclude that in contrast to the increase in diastolic pressure elicited by B-HT 920, calcium channels are not involved in the cirazoline-induced pressor responses in the pithed cat. The activation of the calcium channels by B-HT 920 is already so efficient that it cannot be further enhanced by Bay k 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMedDate not supplied

Veratridine-induced intoxication: an in vitro model for the characterization of anti-ischemic compounds?

Due to the complexity of ischemia-induced cellular dysfunction many different pharmacological approaches have been tested to improve cellular ischemia resistance. However, despite the importance of [Na+]i for ischemia-induced dysfunction, only very few studies have investigated the contribution of the Na+ channel to ischemia-induced failure of intracellular ion homeostasis. Since an activation of Na+ channels by veratridine also results in a failure of intracellular ion homeostasis, the veratridine- and ischemia-induced alterations of cellular function were compared. Moreover, despite the difference in the electrophysiological changes induced by veratridine and ischemia, the possible involvement of a slowly inactivating, less selective Na+ channel in both veratridine- and ischemia-induced cellular dysfunction is discussed. As a conclusion it is suggested that veratridine intoxication could be a helpful in vitro method for the characterization of putative anti-ischemic compounds.

Action Potentials↗

PubMedDate not supplied

Interaction between R 56865 and alpha-adrenoceptors in the pithed rat.

In pithed normotensive rats, the benzothiazolamine derivative R 56865 in high doses exhibits a competitive antagonism of alpha 1-adrenoceptor-mediated vasoconstrictions. The absence of a depression of the maximum of the dose-response curve of ST 587 and the very moderate attenuation of the maximal B-HT 920-induced increase in diastolic blood pressure (BP) confirms the lack of major calcium entry blocking properties of R 56865 for alpha-adrenoceptor-activated calcium channels in vitro. In doses up to 10(-5) mol/kg, the interaction of R 56865 with the sympathetic neurotransmission can solely be explained by alpha 1-adrenoceptor blockade. This was confirmed by the comparable antagonism of the selective alpha 1-adrenoceptor antagonist prazosin in a concentration of 6 x 10(-8) mol/kg. In contrast to the isolated rat aorta, where R 56865 showed an allosteric interaction with the NA binding site on the alpha 1-adrenoceptor, R 56865 acts like an alpha 1-adrenoceptor antagonist of the competitive type in vivo.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Calcium influx-dependent and -independent alpha 1-adrenoceptor-mediated processes of vasoconstriction in vivo do not operate via different alpha 1-adrenoceptor subtypes.

In pithed rats, the selective alpha 1-adrenoceptor agonists St 587 and cirazoline show preponderant calcium influx-dependent and -independent vasoconstriction, respectively. By using these agonists, selective (competitive) antagonists for either process of vasoconstriction were sought. For this purpose, antagonism was analyzed for eight structurally different antagonists (prazosin, BE 2254, AR-C239, R 28935, corynanthine, phentolamine, sulpiride, and chlorpromazine) opposing the pressor responses evoked by cirazoline and St 587. Where pA2 values (-log dose antagonist evoking a twofold shift for the agonist dose-response curve) could be calculated, no significantly different pA2 values against either agonist resulted. However, with respect to the slopes of the Schild plots, deviations from unity were found for prazosin, R 28935, AR-C239, sulpiride, and chlorpromazine, but not uniformly against both agonists. Following treatment with phenoxybenzamine (PB) (30 micrograms/kg) and nifedipine (1 mg/kg), which produced calcium influx-sensitive and -insensitive vasoconstriction to cirazoline, respectively, Schild plots were constructed for BE 2254, prazosin, and chlorpromazine. Using cirazoline as an agonist, unity slopes were now obtained for prazosin and chlorpromazine. The Schild plots of BE 2254 versus cirazoline after PB or nifedipine administration, however, exhibited a slope deviating from unity. For prazosin and chlorpromazine, identical pA2 values still resulted against both processes of vasoconstriction to cirazoline. The results are compatible with the view that alpha 1-adrenoceptors mediating calcium influx-dependent and -independent vasoconstriction in vivo are not distinctly different entities, but are separate recognition sites of the same receptor.

Adrenergic alpha-Antagonists↗