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A Hyman

Publications and source records attributed to A Hyman.

18 recordsLinked to original sources
PubMed1992

Mechanisms of signal transduction for adenosine and ATP in pulmonary vascular bed.

The purpose of the present study was to investigate the contribution of pertussis toxin (PTX)-sensitive guanine nucleotide (G) proteins in the pulmonary vascular response to adenosine and ATP in the intact cat under conditions of controlled pulmonary blood flow and left atrial pressure. Adenosine, ATP, and beta-tau-ATP increased lobar arterial pressure in a dose-dependent manner. The pulmonary vasoconstrictor response to adenosine was abolished by BW 1433U, a specific purinergic receptor (P1) inhibitor, PTX pretreatment, indomethacin, and ONO 3708, a thromboxane A2 (TxA2) receptor antagonist. These data suggest that the pulmonary vasoconstrictor response to adenosine depends on activation of P1 purinergic receptors coupled to PTX-sensitive G proteins and subsequent metabolism of liberated arachidonic acid to form TxA2. Because each blocking agent studied produced similar reductions in the pulmonary vasoconstrictor response to ATP without altering the pulmonary vasoconstrictor response to beta-tau-ATP, the present data suggest that ATP constricts the pulmonary vascular bed, in part, by hydrolysis to adenosine. Moreover, the present study suggests that both A1 purinoceptors that are linked to PTX-sensitive G proteins as well as P2x purinoceptors receptors that are independent of PTX-insensitive G proteins mediate the pulmonary vasoconstrictor response to ATP in vivo.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

L-NAME enhances pulmonary vasoconstriction without inhibiting EDRF-dependent vasodilation.

The purpose of the present study was to determine the influence of NG-nitro-L-arginine methyl ester (L-NAME) on pulmonary vascular responses to endothelium-dependent relaxing factor- (EDRF) dependent and EDRF-independent substances in the pulmonary vascular bed of the anesthetized cat. Because pulmonary blood flow and left atrial pressure were kept constant, changes in lobar arterial pressure directly reflect changes in pulmonary vascular resistance. When pulmonary vasomotor tone was actively increased by intralobar infusion of U-46619, intralobar bolus injections of acetylcholine, bradykinin, serotonin, and 5-carboxyamidotryptamine (a serotonin1A receptor agonist) decreased lobar arterial pressure in a dose-related manner. The pulmonary vasodilator response to serotonin, but not to 5-carboxyamidotryptamine, acetylcholine, and bradykinin, was significantly decreased by L-NAME (100 mg/kg i.v.). Administration of ritanserin (0.5 mg/kg i.v.), but not L-arginine (1 g/kg i.v. with 60 mg.kg-1 x min-1 i.v. infusion), reversed the inhibitory effects of L-NAME on the pulmonary vasodilator response to serotonin and abolished the enhanced pulmonary vasoconstrictor response to (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminoproprane hydrochloride (a serotonin2 receptor agonist) after L-NAME administration. In conclusion, the present experiments suggest that L-NAME inhibits the pulmonary vasodilator response to serotonin by increasing the sensitivity of serotonin2 receptor-mediated vasoconstriction and not by inhibiting EDRF formation. Because the pulmonary vasodilator responses to bolus administration of acetylcholine and bradykinin were not inhibited by L-NAME, these data suggest that L-NAME does not appear to be an adequate probe to study the role of endogenous EDRF in the adult feline pulmonary vascular bed in vivo.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1990

Vasodilator activity of endothelin-1 and endothelin-3: rapid development of cross-tachyphylaxis and dependence on the rate of endothelin administration.

In pentobarbital anesthetized cats, i.v. bolus injections of endothelin-1 (ET-1, 1 microgram) and ET-3 (3 micrograms) produced a rapidly appearing but short-lasting fall in aortic blood pressure followed in the case of ET-1 only by a small pressor response. When these peptides were administered repeatedly after 10- to 12-min intervals, there was a gradual attenuation of the hypotension that by the fourth injection was replaced by a monophasic pressor response. The i.v. infusion of ET-1 (0.3 microgram/min) or ET-3 (0.9 microgram/min) for 20 min produced sole systemic vasoconstriction. The decrease in blood pressure produced by an i.v. bolus injection of ET-1 and ET-3 was no longer observed 5 min after the end of the ET-1 or ET-3 infusion. In contrast, the hypotensive activity of bradykinin was not modified after the depressor responses to ET-1 and ET-3 had disappeared. Thus, the failure of i.v. bolus injections of ET-1 and ET-3 to lower blood pressure under these experimental conditions cannot be attributed to the development of tachyphylaxis to endogenous endothelium-derived relaxant factor, which is known to mediate the effects of bradykinin. These results suggest that ET-1 and ET-3 share a single vascular receptor for vasodilation, which becomes refractory upon repeated or maintained exposure to these peptides. Alternatively, this refractoriness may be due to depletion of an intracellular mediator(s) that is jointly used by the membrane binding sites of ET-1 and ET-3. Moreover, the present data suggest that the vasodilator activity of ETs depends on the rate of the peptide administration.

Animals↗
PubMed1990

Hemodynamic and pharmacological evaluation of the vasodilator and vasoconstrictor effects of endothelin-1 in rats.

In awake normotensive and spontaneously hypertensive rats as well as pentobarbital-anesthetized normotensive rats, endothelin-1 (ET-1, 0.063-0.5 nmol/kg i.v.) produced rapidly appearing, transient, dose-related falls in mean carotid artery blood pressure followed by slowly developing small pressor responses. In the latter preparation, the hypotension was due to a decrease in systemic vascular resistance inasmuch as cardiac output increased slightly. Bilateral vagotomy, BW 755c, glibenclamide, idazoxan, propranolol, methylatropine, methysergide or promethazine pretreatment failed to modify the hypotension induced by ET-1 (0.25 nmol/kg i.v.), but this effect was blocked entirely when ET-1 was injected 8 min after starting an i.v. infusion of ET-1 (0.1 nmol/kg/min for 10 min). In pithed rats, ET-1 (0.125-1.0 nmol/kg i.v.) produced sustained pressor responses which were accompanied by reductions in cardiac output. This peptide (0.25 nmol/kg i.v.) did not affect renal vascular resistance significantly but increased (200%) mesenteric resistance substantially more (3-fold) than systemic or hindquarter resistance. The pressor effects of ET-1 were reduced by diltiazem, nitrendipine, verapamil or cromakalim and unchanged after BW 755c, desipramine, enalapril, indomethacin, methysergide, phentolamine or SK&F 100273. The sustained pressor response evoked by an i.v. infusion of ET-1 (0.25 nmol/kg/min/60 min) was also antagonized markedly by nitrendipine and cromakalim. In pithed rats with vasopressin-supported blood pressure, ET-1 produced a short-lasting hypotension which faded entirely after three successive injections of the peptide. Finally, ET-1 (0.4-0.8 nM) evoked greater contractile responses in rat aortic rings deprived of a functional endothelium than in intact preparations. However, in the latter preparation precontracted with norepinephrine, ET-1, in contrast to acetylcholine, failed to evoke vasorelaxation. In aortic rings, the sustained contractile effects of ET-1 (3.2 nM) were reduced moderately by nitrendipine (50 nM) and markedly by cromakalim (0.8 microM). In contrast, the latter compounds antagonized strongly the contractile response to KCl (25 mM). In conclusion, ET-1 appears to produce active vasorelaxation and vasoconstriction via stimulation of specific receptors on blood vessels. The tolerance to the hypotensive effect of ET-1 may indicate that either the receptor site for ET-1 becomes refractory or, alternatively, it is coupled to easily depletable endogenous hypotensive mediators. Finally, inasmuch as the vasoconstrictor effects of ET-1 can be easily counteracted by calcium antagonists under in vivo but not in vitro conditions, the membrane coupling mechanism for ET-1 may not be exactly the same in conductance or resistance vessels.

Animals↗
PubMed1981

Adrenergic mechanisms in canine intralobar pulmonary arteries and veins.

The responses of canine intralobar pulmonary arteries (IPA) and veins (IPV) to transmural nerve stimulation (TNS), and exogenously administered norepinephrine (NE) were studied to evaluate the alpha-adrenergic neuroeffector system in the canine pulmonary vasculature. IPA and IPV elicited contractions in response to both NE (10(-10) to 10(-5) M) and TNS (0.5-32 Hz, 2 ms duration and delay). The equilibrium (steady state) contractile responses of IPA and IPV to TNS were abolished with the adrenergic neuronal blocking agents guanethidine and bretylium and the depolarization blocking agent tetrodotoxin in concentrations which did not affect the responses to NE or KCl. The contractile responses of IPA and IPV to TNS and NE were reduced in a concentration-dependent way, by the alpha-adrenergic receptor-blocking agents phentolamine, tolazoline and clonidine. The contractile responses of IPA and IPV to TNS and NE were enhanced after inhibition of neuronal reuptake of NE (uptake1) with cocaine, as well as after blockade of extraneuronal reuptake of NE (uptake2) with hydrocortisone. Analysis of the equilibrium responses of the IPA and IPV to TNS and NE with an Arunlakshana-Schild plot to define the concentration of alpha 1-receptor antagonists necessary to double the ED50 for TNS and NE (defined as the pA2), demonstrated that the postsynaptic alpha-receptors of IPV differed from that of IPA. These data support the conclusions that IPA and IPV 1) contain a functional adrenergic innervation and neuroeffector system, 2) contract in response to both TNS and NE, 3) demonstrate the presence of mechanisms for both uptake1 and uptake2 of NE, and 4) IPV contain postsynaptic alpha-receptors that may differ from each other.

Animals↗
PubMed1971

Photo-urticaria.

Explore the source record for details and available documents.

Adult↗
PubMedDate not supplied

Vein of Galen malformation: correlation of clinical presentation, arteriography, and MR imaging.

To test the value of currently proposed angiographic categorizations of vein of Galen malformations and a hypothesis regarding the causes of vein of Galen malformations and of accompanying hydrocephalus, as well as to assess the relative utility of MR imaging and CT in clinical evaluation, we reviewed the clinical and radiologic records of 34 patients with vein of Galen malformations. Patients were divided into two groups on the basis of the angiographic demonstration of either an arteriovenous malformation nidus or a direct arteriovenous fistula to the wall of the vein of Galen or one of its tributaries. Patients with such a nidus (n = 17) could be distinguished from those with arteriovenous fistulas alone (n = 17) on the basis of age at presentation (p less than .01) and presenting symptoms. Venous constraints, thought to be etiologically important, were identified in 31 of 34 patients. The presence or absence of hydrocephalus was explainable by mass effect in only 24 of 32 patients. In seven of 32 cases, no obvious mass effect was seen in the presence of hydrocephalus, but arteriographic evidence of venous hypertension was present in all patients with hydrocephalus. MR provided improved depiction of both arterial and venous anatomy as compared with CT. Parenchymal abnormalities were uncommon. No patients had subarachnoid hemorrhages. We conclude that MR is superior to CT in the clinical evaluation of vein of Galen malformations, that the angiographic finding of a nidus separates patients with vein of Galen malformations into clinical and therapeutically relevant groups, and that simple mass effect on the aqueduct is not an adequate explanation for all cases of hydrocephalus in patients with this disease.

Cerebral Angiography↗