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Biomedical subjects

N Chand

Publications and source records attributed to N Chand.

At least 73 records · Page 4Linked to original sources
PubMed1981

Lipoxygenase pathway and hydroperoxy acids: possible relevance to aspirin-induced asthma and hyperirritability of airways in asthmatics.

The precise mechanisms(s) responsible for airway hyperreactivity to spasmogenic agents (for example, cholinergic stimulants, alpha-adrenergic agonists, histamine, PGF2 alpha and several other nonspecific stimuli) in asthmatics is not known. Substantial evidence exists fo the mediator, as well as modulatory, roles of the products of arachidonic acid metabolism operating via the cyclo-oxygenase pathway in the pathophysiology of lung diseases. Aspirin and other inhibitors of cyclo-oxygenase induce severe bronchospasm and asthmatic attacks in a significant population of asthmatic patients. This adverse effect of aspirin is often attributed to inhibition of the synthesis and release of defensive "modulatory" endogenous prostaglandins (PGD and PGI2?) in the lungs. Thus, removal of their "negative feedback" mechanism on the allergic release of chemical mediators (e.g., histamine and SRS-A: leukotriene C and D) from lung mast cells could lead to an enhancement of the release of mediators and severity of asthmatic attacks. In addition to these mechanisms, recent work suggests the diversion of arachidonic acid (AA) metabolism via the lipoxygenase pathway (especially after cyclo-oxygenase inhibition by aspirin and indomethacin), thereby leading to the formation of a new class of biologically active lipids: hydroperoxy acids (HPETE and HETE), leukotrienes (LTA, B, C, D, E) and SRS or SRS-A (LTC, LTD). The inherent or drug (aspirin)-induced deficiency or blockade of cyclo-oxygenases(s) and/or peroxidases in the lungs (and/or other body tissues, including leukocytes) leading to diversion of AA into the formation and accumulation of SRS (leukotrienes), especially in sensitive individuals, could explain the mechanism of aspirin-induced asthma, and probably the generalized syndrome of aspirin-tolerance. Furthermore, the hydroperoxy acids, leukotrienes, (SRS) may also sensitize receptors for other mediators and common nonspecific irritants, and/or induce airway contractions directly. Collectively, these mechanisms could account for airway hyperreactivity in asthma.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1981

Differential effects of prostaglandins on canine intrapulmonary arteries and veins.

1 The sensitivity and contractility of isolated canine intrapulmonary arteries and veins to a variety of primary prostaglandin compounds was studied.2 Intrapulmonary arteries produced no measurable contractile responses to prostaglandin A(1) (PGA(1)), PGA(2), PGB(1), PGD(2), PGE(1), PGE(2) or to PGF(1alpha). However, high concentrations of both PGB(2) (> 10(-7) M) and PGF(2alpha) (> 10(-6) M) elicited concentrated-related, but weak, contractile responses, measuring only 5-25% of KCl-induced maximum contractions.3 Intrapulmonary arteries, partially contracted by 5-hydroxytryptamine (5-HT), exhibited concentration-related relaxations in response to PGE(1); PGE(2), PGA(1) or PGA(2) produced only weak superimposed contractions.4 In contrast to intrapulmonary arteries, intrapulmonary veins contracted in a concentration-related fashion to all prostaglandins tested, where the contractile sensitivity was (based on EC(50) s and threshold concentrations): PGB(2) > PGB(1) > PGD(2) > PGF(2alpha) > PGA(2) >> PGA(1) > PGF(1alpha) > PGE(2) > PGE(1).5 In terms of the ability to generate maximum contractile responses on intrapulmonary veins, the prostaglandins were also variable, with PGA(2) and PGB(2) being the most potent and PGD(2) the least potent.6 Intrapulmonary veins, partially contracted by 5-HT, exhibited concentration-related relaxations to PGE(1) at low concentrations, followed by secondary contractile responses at higher concentrations.7 Neither PGA(1) nor PGA(2) (3.4 x 10(-8) to 3.4 x 10(-5) M) inhibited or potentiated 5-HT responses of intrapulmonary arteries.8 These data suggest that there are species, regional and major qualitative and quantitative, differences in the responsiveness of intrapulmonary arteries and veins to prostaglandin.

Animals↗
PubMed1981

Reactivity of isolated trachea, bronchus and lung strip of cats of carbachol, 5-hydroxytryptamine and histamine: evidence for the existence of methysergide-sensitive receptors.

1 The reactivity was investigated of cat isolated tracheal chains, bronchial spirals and lung parenchymal strips to carbachol, 5-hydroxytryptamine (5-HT) and histamine. 2 Carbachol and 5-HT produced concentration-dependent contractions of all three tissues, responses to the former drug being selectively blocked by atropine and to the latter by methysergide. 3 Histamine failed to elicit a contractile response from the tracheal or bronchial muscle. However, it induced dose-related concentrations of the lung strips, that were selectively blocked by mepyramine. 4 It is concluded that lung parenchymal strips of cats possess mepyramine-sensitive histamine H1-receptors. Receptors for 5-HT, susceptible to methysergide, occur in the tracheobronchial smooth muscles as well as in lung strips of cats.

Animals↗
PubMed1981

5-Hydroxytryptamine induces relaxation of goat pulmonary veins: evidence for the noninvolvement of M and D-tryptamine receptors.

1 Reactivity of goat isolated pulmonary arteries and veins to a variety of vasoactive agents was investigated. 2 Bradykinin (Bk), acetylcholine (ACh), noradrenaline (NA), prostaglandin A1 (PGA1), PGE2, PGF2 alpha and histamine induced dose-dependent contractile responses on veins; 5-hydroxytryptamine (5-HT) induced veno-relaxation. Angiotensin was virtually inactive. 3 Angiotensin, NA, Bk, histamine and 5-HT produced concentration-dependent contractile responses on the arterial strips; these arteries failed to respond to ACh, PGA1, PGE2 or PGF2 alpha. 4 The pulmonary veno-relaxant response to 5-HT was found to be resistant to propranolol, indomethacin, metiamide, cimetidine, methysergide, atropine and morphine. These findings appear to exclude the involvement of adrenergic mechanisms and prostaglandin generation as well as activation of classical M and D-tryptamine receptors by 5-HT in the goat pulmonary veins. This response may be mediated via a presynaptic inhibitory 5-HT receptor. 5 5-HT-induced arterial contractile responses were antagonized by methysergide, showing the occurrence of classical D receptors in the goat pulmonary artery. 6 It is concluded that differential reactivity of pulmonary arteries and veins to vasoactive agents may play differential role(s) in the pathophysiology of pulmonary disease. 5-HT may exert an antiinflammatory activity in goat pulmonary veins.

Animals↗
PubMed1981

Bradykinin-induced relaxation of renal and pulmonary arteries is dependent upon intact endothelial cells.

When most arteries are removed from mammals and man, the in vitro response to kinins, particularly of helically-cut vascular strips, is usually one of contraction; and often no response is observed. This is in sharp contrast to the in situ arterial vasodilator action of kinins. The reason(s) for this transformation is not known. The present in vitro experiments demonstrate that bradykinin can produce potent relaxation of canine isolated intrapulmonary arteries (threshold concentration = 7.5 +/- 2.7 x 10(-10) M) and renal arteries (threshold concentration = 3.2 +/- 1.6 x 10(-10) M) contracted by phenylephrine, provided the endothelium is left intact. Selective, mechanical destruction of the endothelium transforms the vasodilator activity of bradykinin to either contraction or to no response at all. Our results probably explain why previous investigators have found that bradykinin usually induced contraction, rather than relaxation, of excised peripheral arteries.

Animals↗
PubMed1980

Occurrence of inhibitory histamine H2-receptors in isolated pulmonary blood vessels of dogs and rats.

Isolated, helically cut strips of pulmonary arteries and veins of dogs, and pulmonary arteries of rats, precontracted with norepinephrine or 5-HT exhibited potent concentration-dependent relaxations to impromidine and dimaprit (histamine H2-agonists). The occurrence of inhibitory histamine H2-receptors in the pulmonary vasculature could play a modulatory role in hypoxic pulmonary vasoconstriction.

Animals↗
PubMed1980

Reactivity of isolated rat and canine pulmonary blood vessels to synthetic prostaglandin endoperoxide (PGH2) analogs.

Reactivity and contractility of isolated pulmonary blood vessels of rats and dogs to two synthetic prostaglandin endoperoxide (PGH2) analogs were studied. Canine pulmonary arteries were found to be insensitive to PGH2 analogs (i.e. U-46619 and U-44069) that were tested. In contrast, rat main pulmonary artery (EC50's = 4 x 10(-10)M, respectively) responded to the endoperoxide analogs with potent and concentration-dependent contractile responses. This study demonstrates regional and species-related variability in the reactivity of pulmonary vascular smooth muscles to biologically, highly potent vasoactive agents. Endogenously generated and released PG-endoperoxides (PGH2) may play important roles in the patho-physiology of the pulmonary vasculature.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1980

Reactivity of isolated rat and canine pulmonary arteries to prostaglandins.

In this investigation, the sensitivity and contractility of isolated rat and canine pulmonary arteries to a variety of prostaglandin compounds (PGs) were studied. Based on EC50's and threshold concentrations, the contractile sensitivity of rat pulmonary arteries to PGs was: PGB2 > PGA2 > PGF2 alpha approximately equal to PGE2 > PGB1 approximately equal to PGA1 > PGF1 alpha approximately equal to PGE1 > PGD2. In terms of the ability to generate a maximum contractile responses on rat pulmonary arteries, the PGs were also variable, where PGB2 was the most potent and PGD2 the least potent agonist. None of these contractile responses were tachyphylactic on rat pulmonary arteries. Surprisingly, except for PGB2, none of the PGs elicited reproducible contractile responses on canine pulmonary arteries. The present data, therefore, clearly indicate that there are species differences with respect to the contractile action of PGs on pulmonary vessels. In addition, these findings suggest that a clear structure-activity relationship exists for the contractile action of PGs on rat pulmonary arteries. The latter differential reactivity may be important in hypoxic pulmonary vasoconstriction and allergic hypersensitivity phenomena in certain mammals.

Animals↗
PubMed1980

Is airway hyperactivity in asthma due to histamine H2-receptor deficiency?

The underlying biochemical and physiological changes responsible for remarkable airway hyperreactivity to histamine and other non-specific stimuli in asthmatics are poorly understood. Based on some experimental observations, a hypothesis "Deficiency of histamine H2-receptors in asthma" is proposed. The deficiency of histamine H2-receptor (histamine-sensitive adenyl cyclase) on leukocytes (mast cells, basophils, neutrophils and eosinophils) and in the airway smooth muscles during the process of hypersensitization, immunization, infectious diseases as well as in atopic bronchial asthmatics could occur. The H2-receptor deficiency or physiological imbalance of histamine H1- and H2-receptors in the airways may at least, in part, explain the most commonly observed phenomenon of remarkable airway hyperreactivity to histamine in asthmatics.

Animals↗
PubMed1980

Reactivity of trachea, bronchi, and lung strips to histamine and carbachol in rhesus monkeys.

Responses of isolated airway smooth muscles of a subhuman primate to carbachol and histamine were investigated. Isolated lung parenchymal strips of rhesus monkeys (RM) exhibited approximately equal sensitivity (i.e., ED50) and contractility (i.e., maximum tension) to carbachol and histamine. Tracheal chains and bronchial strips responded with concentration-dependent contractions to carbachol. Trachea did not exhibit any contractile responses to histamine. Bronchial strips responded with weak contractile responses to histamine when compared with those elicited ay carbachol. Histamine-induced contractions on bronchi and lung strips were easily antagonized by pyrilamine (H1-receptor antagonist) (10(-6) to 5 X 10(-6) M). Carbachol-contracted trachea and bronchi responded with relaxations to histamine and dimaprit (H2-receptor agonist) that were antagonized by metiamide (H2-receptor antagonist) (5 X 10(-5) M). The present findings indicate 1) a differential reactivity of central and peripheral airway smooth muscles of RM to histamine and carbachol; 2) lung strips of RM appear to possess only H1 types of histamine receptors; 3) bronchial smooth muscles of RM have a small population of H1-receptors mediating bronchoconstriction; and 4) a preponderance of inhibitory H2-receptors in the tracheobronchial smooth muscles of rhesus monkeys. If these subhuman primate findings apply to the airways of man, they could aid considerably in furthering our understanding of the pathophysiology of the respiratory tract.

Animals↗
PubMed1980

Reactivity and contractility of rat main pulmonary artery to vasoactive agents.

In vitro studies were undertaken to determine the reactivity and contractility of the rat main pulmonary artery (RPA) to some selected vasoactive agents. Oxytocin was found to be inactive RPA exhibited a poor responsiveness to vasopressin, acetylcholine, histamine, and bradykinin. Prostaglandins B2 and E2, K+, angiotensin, sympathomimetic agents (epinephrine and isoproterenol), 5-hydroxytryptamine (5-HT), and [Ca2+]0 were found to produce, consistently, potent and concentration-related contractions of the RPA. Pulmonary arterial strips that were precontracted with 5-HT responded with relaxations to isoproterenol in low concentrations and with contractions in high concentrations. Blockade of isoproterenol-induced relaxation by propranolol provides evidence for the existence of specific beta-adrenoceptors in RPA. The selective antagonism of contractile responses induced by epinephrine, 5-HT, acetylcholine, and histamine by phentolamine, methysergide, atropine, and pyrilamine, respectively, provides evidence for the occurrence of specific alpha-adrenergic, "D"-serotonin as well as some cholinergic (muscarinic) and H1-histamine receptors in the RPA.

Animals↗
PubMed1980

Acute systemic anaphylaxis in adult domestic fowl: evidence for the protective role of H2-histaminergic and beta 2-adrenergic receptors.

Pentobarbital-anesthetized and spontaneously breathing, bovine albumin (BA)-sensitized adult domestic fowl showed acute systemic anaphylaxis to IV injection of antigen (BA), which was characterized by arterial hypotension, central venous hypertension, and bradycardia. Large doses of pyrilamine maleate (/1-receptor antagonist) partially inhibited acute systemic anaphylaxis. On the other hand, metiamide (a specific H2-antagonist) and propranolol (beta-adrenergic antagonist) markedly enhanced the anaphylactic response. Terbutaline (beta 2-agonist), dimaprit (a highly selective H2-agonist), and compound FPL 55712 (a slow-reacting substance of anaphylaxis receptor antagonist) either significantly inhibited or reversed the anaphylactic response. Cimetidine (a newer H2-antagonist) enhanced only central venous pressor response to BA. This investigation appears to suggest a minor role of histamine and a major role of slow-reacting substance of anaphylaxis as chemical mediatiors of anaphylaxis. A protective role of beta 2-adrenergic and H2-histaminergic receptors seem to operate in immediate hypersensitivity reactions in adult domestic fowl.

Anaphylaxis↗
PubMed1980

Further studies of dog tracheobronchial smooth muscle.

Isolated canine tracheal and bronchial smooth muscle contracted to carbachol, 5-HT and histamine. PGF2 alpha and bradykinin were inactive. Carbachol-contracted airway smooth muscle relaxed to PGE1, PGE2, isoproterenol, dimaprit (H2-agonist) and bradykinin (BK). Indomethacin blocked relaxations to BK. Mepyramine in low doses specifically antagonized contractions to histamine. Mepyramine-resistant contractions to histamine were blocked by atropine and burimamide. In the presence of mepyramine (after H1-blockade), relatively high doses of histamine relaxed bronchi (but not tracheas) which were submaximally contracted to carbachol. Bronchial relaxations to histamine were resistant to indomethacin and propranolol suggesting that prostaglandin and catecholamine release mechanisms were not involved. Burimamide (H2-antagonist) enhanced broncho-relaxant effects of histamine and attenuated relaxations to isoproterenol and contractions to carbachol. This investigation showed a preponderance of H1-histamine receptors in canine airways and a small population of H2 (inhibitory) histamine receptors, partially resistant to H2-antagonism.

Airway Resistance↗
PubMed1980

In vitro peripheral airway constriction to honey bee venom in cat.

Isolated lung parenchymal strips (peripheral airways) of cats responded to histamine, carbachol, 5-HT, bradykinin and honey bee-venom with concentration-dependent contractions. Atropine, mepyramine and methysergide inhibited or reversed contractions to carbachol, histamine and 5-HT respectively. Atropine, methysergide and indomethacin did not influence contractions to honey bee venom. High doses of mepyramine (H1-antagonist) inhibited or reversed the bee venom-induced contractions. These observations suggest that honey bee venom may be constricting cat peripheral airways by releasing endogenous histamine from the lung mast cells. Aceylcholine, 5-HY and prostaglandins appear to play little or no important role in the peripheral airway constrictions to honey bee venom in cat.

Animals↗
PubMed1980

Serotonin receptors subserve only contraction in canine and rat pulmonary arteries and veins.

Precise information with respect to whether serotonin (5-HT) exerts direct effects on mammalian pulmonary arteries and veins is lacking. The present studies, using isolated pulmonary arterial strips of dogs and rats, as well as isolated pulmonary veins of dogs, indicate that serotonin exerts direct contractile, but not relaxant, effects on these blood vessels. Contractile responses to 5-HT were not influenced by "specific" receptor-blocking doses of pyrilamine (H1-receptor antagonist), metiamide (H2-receptor antagonist), phentolamine (alpha-adrenoceptor antagonist), propranolol (beta-receptor antagonist), atropine (cholinergic antagonist) or morphine ("M" tryptamine antagonist). These data demonstrate the lack of interaction of 5-HT with either H1- and H2-histamine, alpha and beta-adrenergic, cholinergic, or "M" tryptamine receptors in these pulmonary blood vessels. Selective, competitive antagonism of 5-HT-induced contractions by methysergide (parallel shifts of concentration-effect curves) demonstrate a direct action of 5-HT on D-type serotonin receptors in these pulmonary blood vessels.

Animals↗