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R J Altiere

Publications and source records attributed to R J Altiere.

49 records · Page 3Linked to original sources
PubMed1984

Neural control of relaxation in cat airways smooth muscle.

Functional innervation of cat airways smooth muscle was examined in isolated segments of trachea and bronchi using electrical field stimulation (EFS) techniques. Field stimulation caused contraction in tissues at resting tone and biphasic responses (contraction followed by relaxation) in tissues precontracted with 5-hydroxytryptamine (5-HT). Contractions were abolished by 10(-6) M atropine. Inhibitory responses were dependent on impulse voltage, duration, and frequency. At low voltages (less than or equal to 10 V) and pulse durations (less than or equal to 0.3 ms), EFS induced relaxations were abolished by 3 X 10(-6) M tetrodotoxin (TTX). Greater stimulus parameters elicited TTX-resistant relaxations. Pretreatment of the tissues with 10(-6) M propranolol and 10(-5) M guanethidine caused rightward shifts in relaxation frequency-response curves. These findings indicate that cat airways are innervated by excitatory cholinergic, inhibitory adrenergic, and inhibitory nonadrenergic noncholinergic (NANC) nerves. Pretreatment of the tissues with hexamethonium, cimetidine, indomethacin, or nordihydroguaiaretic acid did not affect NANC relaxation responses. It is concluded that NANC inhibitory responses in cat airway smooth muscle are mediated through intrinsic postganglionic nerve fibers and occur independently of histamine H2-receptor activation and without involvement of cyclooxygenase or lipoxygenase products of arachidonic acid metabolism.

Animals↗
PubMed1983

Relaxant effects of vasoactive intestinal peptide and bethanechol in cat intrapulmonary artery.

The relaxant actions of vasoactive intestinal peptide (VIP) and bethanechol were examined on ring segments of intrapulmonary artery (IPA) isolated from cat lung. On a molar basis, VIP was 75 times more potent than bethanechol; however, VIP was less efficacious than bethanechol in reversing phenylephrine induced tone. Responses to VIP were unaffected by pretreatment of the tissues with atropine, indomethacin or avian pancreatic polypeptide. These results suggest that VIP may participate in the regulation of pulmonary vascular smooth muscle tone through a potent relaxant action that occurs independent of muscarinic cholinergic receptor activation or liberation of prostaglandins.

Animals↗
PubMed1983

In vivo bronchodilator activity of vasoactive intestinal peptide in the cat.

Vasoactive intestinal peptide (VIP) is an octacosapeptide that occurs widely in the animal kingdom, is distributed in many organs and tissues, and has a broad range of biologic actions. We evaluated the ability of VIP to produce bronchodilation in anesthetized, mechanically ventilated, atropinized, closed chest cats. Boluses of VIP injected intravenously (0.1 to 10 micrograms X kg-1) reversed in a dose-dependent manner the increase in lung resistance (RL) and the decrease in dynamic lung compliance (Cdyn) induced by an intravenously administered infusion of 5-hydroxytryptamine (5HT) (5 to 30 micrograms X kg-1 X min-1). Distribution of bronchodilator activity was assessed by using RL as an index of central airways caliber and dynamic elastance (Edyn; the inverse of Cdyn) as an index of tone in peripheral airways and lung parenchyma. Although all levels of the tracheobronchial tree responded to VIP, the predominant site of action appeared to be in central airways. A similar distribution and magnitude of relaxant effects were observed after the intravenous administration of prostaglandin E2 (PGE2) (0.1 to 10 micrograms X kg-1). Prostaglandin E2 also was effective in reversing 5HT-induced bronchoconstriction when given by ultrasonic nebulization, whereas VIP was not. Bronchodilation mediated by VIP persisted after pretreatment with indomethacin or propranolol. We conclude that VIP is a potent relaxant of feline airways smooth muscle in vivo and that this effect of the peptide occurs independent of prostaglandin production or beta adrenergic receptor activation.

Animals↗
PubMed1983

Potassium chloride- and norepinephrine-induced contractile responses in rabbit pulmonary blood vessels.

Responses to KCl and norepinephrine (NE) were examined with ring segments of right extrapulmonary artery, intrapulmonary artery and intrapulmonary vein isolated from rabbit lung. From concentration-response curves to KCl, optimal applied loads were determined to be 5 g for right extrapulmonary artery and intrapulmonary artery and 500 mg for intrapulmonary vein. Both individual and cumulative concentration-response curves to KCI and NE were performed. All gave reproducible results; however, tissues were more sensitive to cumulative addition of either contractile agent. Of three successive cumulative NE concentration-response curves, second and third curves were most reproducible in relation to both sensitivity to NE and maximal force development. Cumulative NE concentration-response curves also exhibited a triphasic pattern, consisting of an initial contractile response (10(-10) to 10(-6) M NE) followed by relaxation or reversal of contractile force development (10(-6) to 10(-4) M NE), then a second contractile response at concentrations of NE greater than 10(-4) M. This response pattern was most prominent in intrapulmonary vessels and was absent in rabbit aorta.

Animals↗
PubMed1983

Pharmacological analysis of norepinephrine responses in rabbit pulmonary blood vessels.

Drug effects were examined on cumulative norepinephrine (NE) concentration-response curves in ring segments of right extrapulmonary artery, intrapulmonary artery (IPA) and intrapulmonary vein (IPV) isolated from rabbit lung. Phentolamine (0.1 and 1.0 microM) caused concentration-dependent nonparallel rightward shifts in NE concentration-response curves and decreased maximal tension development in IPA by as much as 84%. Propranolol (3 microM) significantly increased the maximal developed tension to NE in IPA and IPV by 49 and 27%, respectively, and also abolished the relaxation response to higher (10(-6) to 10(-4) M) concentrations of NE observed in control experiments. These data suggested that responses of pulmonary vessels to NE, in particular IPA and IPV, consisted of an initial contractile response (alpha adrenergic receptor mediated) followed by beta adrenergic receptor-mediated relaxation which functionally opposed the contractile response to NE. Contractile response to high concentrations of NE (greater than 10(-4) M) were unaffected. Inhibition of neuronal uptake of NE by cocaine (10 microM) significantly potentiated NE contractile response in right extrapulmonary artery, IPA and IPV. Inhibition of extraneuronal uptake of NE by hydrocortisone (30 microM) or monoamine oxidase inhibition by harmaline (1 microM) did not alter contractile response to NE. Although the catechol-O-methyl-transferase inhibitor U-0521 (100 microM) also failed to potentiate NE contractile effects, this drug significantly decreased the initial contractile response to low concentrations of NE and greatly attenuated contractile responses to high concentrations of NE (greater than 10(-4) M) in IPA and IPV. These results indicate that rabbit intrapulmonary vessels show enhanced beta adrenergic receptor-mediated effects when compared with extrapulmonary vessels.

Animals↗
PubMed1982

Uptake and displacement of [3H]dihydroalprenolol, [3H]epinephrine and [3H]clonidine in isolated perfused rabbit lung.

Uptake and displacement of three adrenergic receptor ligands, [3H]dihydroalprenolol ([3H]DHA), [3H]epinephrine ([3H]EPI) and [3H]clonidine ([3H]CLON), were examined in isolated rabbit lungs by recirculating perfusion. Removal of [3H]DHA was the most extensive (85% uptake; 6.6 ml/min clearance), [3H]CLON removal was intermediate (50%; 3.8 ml/min), and [3H]EPI removal was the lowest (33%; 1.2 ml/min). Specific displacement of each radioligand from lung was attempted using several competing agents. Both (--)- and (+)-propranolol equally displaced [3H]DHA from lung. Phentolamine, (--)-phenylephrine and (--)-epinephrine were unable to displace 10 nM [3H]EPI from lung, although the latter two agents did produce concentration-dependent increases in perfusion pressure. High concentrations of (--)-epinephrine, which produced near maximal physiological responses, inconsistently displaced 30-4- nM [3H]EPI from lung. [3H]Clonidine was displaced by unlabeled clonidine at concentrations that caused increases in perfusion pressure. Pretreatment of lungs with either 10 microM phentolamine or phenoxybenzamine did not alter the total amount of [3H]CLON displaced by clonidine, suggesting that [3H]CLON was displaced predominantly from non-specific sites, perhaps preventing detection of [3H]CLON displacement from specific (receptor) sites. Alternatively, these results may be interpreted as inhibition of uptake of each radioligand. Thus, both (--)- and (+)-propranolol interfered with [3H]DHA removal, suggesting a common mechanism for uptake and/or retention for these two beta-adrenergic receptor antagonists. Inhibition of [3H]EPI removal was observed only at high concentrations of (--)-epinephrine which indicates that pulmonary removal of epinephrine occurs through a low affinity uptake system. [3H]Clonidine removal was effectively inhibited by the same (microM) concentrations of unlabeled clonidine that produced physiological responses. Neither phentolamine nor phenoxybenzamine was able to interfere with pulmonary removal of [3H]CLON. Therefore, uptake and displacement of these adrenergic receptor radioligands showed no correlation with pharmacological effects produced by these agents in isolated perfused rabbit lung. The results are more closely associated with inhibition of removal and/or non-specific retention of the radioligands examined.

Alprenolol↗
PubMed1981

Temperature related effects on the binding characteristics of beta-adrenergic receptor agonists and antagonists by rabbit lung.

The effects of incubation temperature on binding characteristics of beta-adrenergic receptor agonists and antagonists were examined in rabbit whole lung membrane fragments. [3H] Dihydroalprenolol ([3H] DHA) exhibited single component, non-cooperative binding at 37 degrees C and 25 degrees C with characteristics representative of beta-adrenergic receptors. Inhibition of [3H] DHA binding by l-propranolol showed single component binding at either incubation temperature, but with slightly higher affinity at 25 degrees C, when analyzed by Hofstee plots. The binding of l-isoproterenol, l-epinephrine and l-norepinephrine were changed qualitatively, as well as quantitatively, by incubation temperature. Hofstee plot analysis of l-isoproterenol inhibition curves showed a linear plot at 37 degrees C and a curvilinear plot at 25 degrees C, whereas l-epinephrine and l-norepinephrine showed curvilinear plots at both temperatures, but with different relative distributions and affinities of the components. The binding characteristics of several selective beta 1- and beta 2-agonists and antagonists were also influenced by incubation temperature. Practolol and prenalterol, beta 1-selective agents, exhibited multiple component binding at 25 degrees C, but only single component binding at 37 degrees C. In contrast, salbutamol, a beta 2-selective agonist, showed single component binding at 25 degrees C and apparent multiple component binding at 37 degrees C. Such temperature-related changes in binding characteristics were not consistent with receptor subtype interconversion and were not restricted to either agonists or antagonists. These studies suggest that the choice of incubation temperature may result in different binding characteristics of various beta-adrenergic receptor ligands. These effects are especially important when binding studies are designed to determine the classification and density of beta-adrenergic receptor subtypes in individual tissues.

Adrenergic beta-Agonists↗
PubMed1981

Inhibition of actomyosin superprecipitation by an indole derivative of epinephrine.

A zwitterion indole metabolite of epinephrine, an inhibitor of actomyosin ATPase, has been shown to delay or prevent superprecipitation of cardiac and skeletal muscle actomyosin in a concentration-dependent manner. Inhibition of superprecipitation was not solely dependent on inhibition of actomyosin ATPase activity, suggesting that the ATPase inhibitor directly interfered with interaction of actin and myosin. Such an effect may occur by attachment of the indole derivative to free sulfhydryl groups involved in actin-myosin association as previously postulated for inhibition of ATPase activity.

Actomyosin↗
PubMedDate not supplied

The effects of antagonists of vasoactive intestinal peptide on nonadrenergic noncholinergic inhibitory responses in feline airways.

Relaxations of the feline intrapulmonary bronchus (IPB) induced by VIP or nonadrenergic noncholinergic (NANC) inhibitory nervous stimulation were unaffected by the VIP receptor antagonist [Ac-Tyr1,D-Phe2]-GRF (1-29) (30 microM). A second VIP antagonist, [pCl-D-Phe6,Leu17]-VIP (30 microM), also had no effect on NANC relaxation responses or IPB sensitivity to VIP. However, responses to three of the four highest VIP concentrations were inhibited by this antagonist. These results indicate that [Ac-Tyr1,D-Phe2]-GRF (1-29) and [pCl-D-Phe6,Leu17]-VIP are not effective competitive antagonists of VIP receptors in feline airways and, hence, have but limited applicability in determining the role of VIP in mediating airway NANC inhibitory responses in this tissue.

Acetylcholine↗