Characterization of H1- and H2-receptor function in pulmonary and systemic circulations of sheep

1982 ◽  
Vol 53 (1) ◽  
pp. 175-184 ◽  
Author(s):  
T. Ahmed ◽  
K. B. Mirbahar ◽  
W. Oliver ◽  
P. Eyre ◽  
A. Wanner
Keyword(s):  
Vascular Tone ◽  
Base Line ◽  
H2 Receptor ◽  
Receptor Response ◽  
H2 Antagonist ◽  
H2 Receptors ◽  
H1 Antagonist ◽  
Vasodepressor Response

We investigated the histamine H1- and H2-receptor function in the pulmonary and systemic circulations of sheep by in vivo and in vitro techniques. Combined H1 and H2 stimulation (by intravenous histamine) in vivo increased pulmonary vascular resistance (PVR) to 435% of base line and decreased systemic vascular resistance (SVR) to 49% of base line. Selective H2 stimulation (histamine after chlorpheniramine pretreatment) decreased PVR and SVR to 86 and 82% at base line, respectively, while selective H1 stimulation (histamine after metiamide pretreatment) increased PVR to 424% of base line and decreased SVR to 64% of base line. Combined H1- and H2-antagonist pretreatment completely blocked the effects of histamine on SVR, while PVR still decreased to 85% of base line, suggesting a mild “atypical” H2-receptor response in the pulmonary circulation under conditions of resting vascular tone. With increased pulmonary vascular tone (hypoxia), histamine decreased PVR to 55% (H1-antagonist pretreatment) and to 58% (combined H1- and H2-antagonist pretreatment) of posthypoxia values, respectively, demonstrating a marked atypical H2-receptor response. In vitro, both pulmonary arterial and venous strips showed a contractile dose-response to histamine, which was blocked by the H1-antagonist pyrilamine (mepyramine). In precontracted strips, both histamine and the H2-agonists (dimaprit and impromidine) elicited a relaxant response, which was neither blocked by H1-antagonist alone nor by combined H1- and H2-antagonists. We conclude that in sheep the histamine-induced pulmonary vasoconstrictor response is mediated by H1-receptors, while the pulmonary vasodepressor response is mediated by atypical H2-receptors. The systemic vasodepressor response is mediated by both H1- and typical H2-receptors.

Suppression of pulmonary and systemic vascular histamine H2-receptors in allergic sheep

1986 ◽  
Vol 60 (3) ◽  
pp. 791-797 ◽  
Author(s):  
T. Ahmed ◽  
M. King
Keyword(s):  
Vascular Resistance ◽  
Histamine Receptor ◽  
Base Line ◽  
Group 14 ◽  
H2 Antagonist ◽  
H2 Receptors ◽  
Pulmonary Arterial ◽  
Histamine Response ◽  
H1 Antagonist ◽  
Vasodepressor Response

We have previously demonstrated a depression of airway H2-receptor function in sheep allergic to Ascaris suum antigen. To investigate whether this is a generalized defect, we studied the H1- and H2- histamine receptor functions in the pulmonary and systemic circulations of allergic and nonallergic sheep. Pulmonary arterial pressure, and cardiac output were measured for calculation of pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) before and immediately after a rapid intrapulmonary infusion of histamine (10 micrograms/kg), with and without pretreatment with H1- (chlorpheniramine) and H2- (metiamide) antagonists. Histamine alone increased mean PVR to 435 and 401% of base line and decreased mean SVR by 51 and 54% in the nonallergic and allergic sheep, respectively (P less than 0.001). In the nonallergic sheep following pretreatment with chlorpheniramine (selective H2 stimulation) or metiamide (selective H1 stimulation), histamine decreased SVR by 18 and 36%, respectively, suggesting that approximately two-thirds of the vasodepressor response was mediated by H1-receptors and one-third by H2-receptors. Combined H1- and H2-antagonists completely blocked the histamine response. In allergic sheep the histamine-induced decrease in SVR was primarily mediated by H1-receptors, because the response was blocked by H1-antagonist, chlorpheniramine, and the H2-antagonist, metiamide, had no effect. In the pulmonary circulation selective H1-stimulation caused a similar increase in PVR in allergic (365%) and nonallergic sheep (424%), whereas selective H2-stimulation caused a significant decrease in PVR in the nonallergic group (14%) but not in the allergic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration of histamine response by H2-receptor antagonism in the guinea pig

1980 ◽  
Vol 48 (4) ◽  
pp. 613-618 ◽  
Author(s):  
J. M. Drazen ◽  
C. S. Venugopalan ◽  
M. W. Schneider
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Fold Increase ◽  
H2 Receptor Antagonist ◽  
Receptor Antagonism ◽  
H2 Receptor ◽  
H2 Receptors ◽  
Histamine Response

Effects of H2-receptor antagonism on the response to histamine was studied in the guinea pig in vivo and in vitro. The H2-receptor antagonist, metiamide (100 micro M), resulted in an enhanced histamine response in eight of eight parenchymal strips and in four of eight tracheal spirals. On the average the parenchymal strips were 20-fold more sensitive to histamine (P less than 0.001), whereas the tracheal spirals demonstrated an insignificant, 20%, increase in sensitivity after metiamide treatment. These results are consistent with the hypothesis that there are inhibitory H2-receptors in guinea pig airways and they predominate in the periphery. When we determined the effects of H2-antagonism on the histamine response in vivo we found that the histamine response was enhanced only in animals that had been treated with the beta-receptor antagonist propranolol. In these animals there was a mean 2.2-fold increase in histamine sensitivity. These results suggest that although there are inhibitory H2-receptors in the guinea pig lung, their role in modulating the in vivo response is much less than beta-adrenergic mechanisms.

scholarly journals PRESENCE OF A BASE LINE LEVEL OF SISTER CHROMATID EXCHANGES IN SOMATIC CELLS OF DROSOPHILA MELANOGASTER IN VIVO AND IN VITRO

Genetics ◽  
1982 ◽  
Vol 100 (2) ◽  
pp. 259-278
Author(s):  
Hideo Tsuji
Keyword(s):  
Drosophila Melanogaster ◽  
Sister Chromatid ◽  
Ganglion Cells ◽  
Sister Chromatid Exchanges ◽  
Base Line ◽  
Cell Cycles ◽  
Chromatid Exchanges ◽  
Third Instar Larvae

ABSTRACT Sister chromatid exchanges (SCEs) under in vivo and in vitro conditions were examined in ganglion cells of third-instar larvae of Drosophila melanogaster (Oregon-R). In the in vivo experiment, third-instar larvae were fed on synthetic media containing 5-bromo-2′-deoxyuridine (BrdUrd). After two cell cycles, ganglia were dissected and treated with colchicine. In the in vitro experiment, the ganglia were also incubated in media containing BrdUrd for two cell cycles, and treated with colchicine. SCEs were scored in metaphase stained with Hoechst 33258 plus Giemsa. The frequencies of SCEs stayed constant in the range of 25-150 vg/ml and 0.25-2.5 vg/ml of BrdUrd in vivo and in vitro, respectively. SCEs gradually increased at higher concentrations, strongly suggesting that at least a fraction of the detected SCEs are spontaneous. The constant levels of SCE frequency were estimated, on the average, at 0.103 per cell per two cell cycles for females and 0.101 for males in vivo and at 0.096 for females and 0.091 for males in vitro. No difference was found in the SCE frequency between sexes at any of the BrdUrd concentrations. The analysis for the distribution of SCEs within chromosomes revealed an extraordinarily high proportion of the SCEs at the junctions between euchromatin and heterochromatin; the remaining SCEs were preferentially localized in the euchromatic regions of the chromosomes and in the heterochromatic Y chromosome. These results were largely inconsistent with those of Gatti et al. (1979).

Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release

1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Gonadal Hormone ◽  
Base Line ◽  
Pituitary Cells ◽  
Intact Male ◽  
Castrate Male ◽  
Basal Release

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function

2002 ◽  
Vol 82 (1) ◽  
pp. 131-185 ◽  
Author(s):  
Richard J. Roman
Keyword(s):  
Arachidonic Acid ◽  
Angiotensin Ii ◽  
Vascular Tone ◽  
Mesangial Cells ◽  
Cardiovascular Function ◽  
Tubuloglomerular Feedback ◽  
Peripheral Vasculature ◽  
Therapeutic Benefits

Recent studies have indicated that arachidonic acid is primarily metabolized by cytochrome P-450 (CYP) enzymes in the brain, lung, kidney, and peripheral vasculature to 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) and that these compounds play critical roles in the regulation of renal, pulmonary, and cardiac function and vascular tone. EETs are endothelium-derived vasodilators that hyperpolarize vascular smooth muscle (VSM) cells by activating K+channels. 20-HETE is a vasoconstrictor produced in VSM cells that reduces the open-state probability of Ca2+-activated K+channels. Inhibitors of the formation of 20-HETE block the myogenic response of renal, cerebral, and skeletal muscle arterioles in vitro and autoregulation of renal and cerebral blood flow in vivo. They also block tubuloglomerular feedback responses in vivo and the vasoconstrictor response to elevations in tissue Po2both in vivo and in vitro. The formation of 20-HETE in VSM is stimulated by angiotensin II and endothelin and is inhibited by nitric oxide (NO) and carbon monoxide (CO). Blockade of the formation of 20-HETE attenuates the vascular responses to angiotensin II, endothelin, norepinephrine, NO, and CO. In the kidney, EETs and 20-HETE are produced in the proximal tubule and the thick ascending loop of Henle. They regulate Na+transport in these nephron segments. 20-HETE also contributes to the mitogenic effects of a variety of growth factors in VSM, renal epithelial, and mesangial cells. The production of EETs and 20-HETE is altered in experimental and genetic models of hypertension, diabetes, uremia, toxemia of pregnancy, and hepatorenal syndrome. Given the importance of this pathway in the control of cardiovascular function, it is likely that CYP metabolites of arachidonic acid contribute to the changes in renal function and vascular tone associated with some of these conditions and that drugs that modify the formation and/or actions of EETs and 20-HETE may have therapeutic benefits.

Tracheal smooth muscle mechanics in vivo

1990 ◽  
Vol 68 (1) ◽  
pp. 209-219 ◽  
Author(s):  
M. Okazawa ◽  
P. Pare ◽  
J. Road
Keyword(s):  
Smooth Muscle ◽  
Muscle Mechanics ◽  
Muscle Length ◽  
Base Line ◽  
Maximal Velocity ◽  
Velocity Of Shortening ◽  
Length Changes ◽  
Trachealis Muscle

We applied the technique of sonomicrometry to directly measure length changes of the trachealis muscle in vivo. Pairs of small 1-mm piezoelectric transducers were placed in parallel with the muscle fibers in the posterior tracheal wall in seven anesthetized dogs. Length changes were recorded during mechanical ventilation and during complete pressure-volume curves of the lung. The trachealis muscle showed spontaneous fluctuations in base-line length that disappeared after vagotomy. Before vagotomy passive pressure-length curves showed marked hysteresis and length changed by 18.5 +/- 13.2% (SD) resting length at functional residual capacity (LFRC) from FRC to total lung capacity (TLC) and by 28.2 +/- 16.2% LFRC from FRC to residual volume (RV). After vagotomy hysteresis decreased considerably and length now changed by 10.4 +/- 3.7% LFRC from FRC to TLC and by 32.5 +/- 14.6% LFRC from FRC to RV. Bilateral supramaximal vagal stimulation produced a mean maximal active shortening of 28.8 +/- 14.2% resting length at any lung volume (LR) and shortening decreased at lengths above FRC. The mean maximal velocity of shortening was 4.2 +/- 3.9% LR.S-1. We conclude that sonomicrometry may be used to record smooth muscle length in vivo. Vagal tone strongly influences passive length change. In vivo active shortening and velocity of shortening are less than in vitro, implying that there are significant loads impeding shortening in vivo.

Histamine H2-receptor of human and rabbit parietal cells

1987 ◽  
Vol 253 (4) ◽  
pp. G497-G501 ◽  
Author(s):  
R. Leth ◽  
B. Elander ◽  
U. Haglund ◽  
L. Olbe ◽  
E. Fellenius
Keyword(s):  
Dose Response ◽  
In Vivo Model ◽  
Response Curves ◽  
Gastric Glands ◽  
Histamine H2 Receptor ◽  
Receptor Affinity ◽  
H2 Receptor ◽  
Dose Response Curves

The histamine H2-receptor on the human parietal cell has been characterized by using dose-response curves and the negative logarithm of the molar concentration of an antagonist (pA2) analyses of cimetidine antagonism of betazole, histamine, and impromidine stimulation in isolated human and rabbit gastric glands. To evaluate the in vitro results, betazole-stimulated gastric acid secretion with and without cimetidine was also studied in healthy subjects. In the in vivo model, individual dose-response curves were shifted to the right with increasing cimetidine concentrations, but this was counteracted by increasing betazole doses, indicating competitive, reversible antagonism. The pA2 values ranged from 6.1 to 6.3. In isolated human gastric glands, impromidine was shown to be eight times more potent than histamine, indicating higher receptor affinity, but the maximally stimulated aminopyrine accumulation was the same as for histamine, and the pA2 values for cimetidine antagonism did not differ significantly, i.e., 5.7 (histamine) and 6.1 (impromidine). In isolated rabbit gastric glands, cimetidine inhibited the histamine- and impromidine-stimulated response with pA2 values of 6.0 and 7.3, respectively. Impromidine was shown to be approximately 100 times more potent than in human gastric glands, whereas histamine had the same potency. This confirms the role of the histamine H2-receptor and suggests a difference between the species concerning receptor affinity.

Effect of histamine on microvascular permeability in the rat stomach

1983 ◽  
Vol 245 (2) ◽  
pp. G201-G207
Author(s):  
H. Nagata ◽  
P. H. Guth
Keyword(s):  
Histamine Receptors ◽  
Microvascular Permeability ◽  
In Vivo Microscopy ◽  
Rat Stomach ◽  
Serosal Surface ◽  
H2 Antagonist ◽  
H1 Antagonist ◽  
Dose Dependent ◽  
Muscularis Externa

The effect of histamine on gastric microvascular permeability to macromolecules in the rat was studied using fluorescent in vivo microscopy. Histamine was applied topically to the serosal surface for study of the muscularis externa, to the submucosa, and to the superficial mucosa, and the area of leaks of a fluorescein-albumin conjugate from microvessels was quantitated. In the muscularis externa both histamine and an H1-agonist, but not an H2-agonist, caused dose-dependent leak of conjugate from venules. An H1-antagonist, but not an H2-antagonist, decreased the histamine-induced leak. In the submucosa histamine caused dose-dependent dilatation of arterioles but not leak of conjugate. In contrast, bradykinin caused both dose-dependent dilatation of arterioles and leak of conjugate from venules. In the superficial mucosa histamine did not cause any leak. In conclusion, topical histamine 1) increased microvascular permeability to macromolecules from venules in the muscularis externa via H1-receptors, 2) did not affect microvascular permeability in the submucosa (this may be due to lack of histamine receptors on the venules as bradykinin increased venular permeability), and 3) did not affect microvascular permeability in the superficial mucosa, but there might not have been adequate histamine backdiffusion.

Influence of SIN-1 on Platelet Ca2+ Handling in Patients with Suspected Coronary Artery Disease: Ex Vivo and In Vitro Studies

2000 ◽  
Vol 83 (05) ◽  
pp. 752-758 ◽  
Author(s):  
Claude Le Feuvre ◽  
Annie Brunet ◽  
Thuc Do Pham ◽  
Jean-Philippe Metzger ◽  
André Vacheron ◽  
...  
Keyword(s):  
Superoxide Anion ◽  
Vascular Tone ◽  
Ex Vivo ◽  
Suspected Coronary Artery Disease ◽  
In Vitro Studies ◽  
H2o2 Formation ◽  
Artery Disease ◽  
Dose Dependent

SummaryThe 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and superoxide anion (O2−). It elicits dose-dependent vasodilation in vivo, in spite of the opposite effects of its breakdown products on vascular tone and platelet aggregation.This study was designed to investigate the influence of intravenous SIN-1 injection on platelet Ca2+ handling in patients undergoing coronary angiography. SIN-1 administration reduced cytosolic [Ca2+] in unstimulated platelets by decreasing Ca2+ influx. It attenuated Ca2+ mobilization from internal stores evoked by thrombin or thapsigargin. In vitro studies were used as an approach to investigate how simultaneous productions of NO and O2− from SIN-1 modify thrombin- or thapsigargin-induced platelet Ca2+ mobilization. Superoxide dismutase, the O2− scavenger, enhanced the capacity of SIN-1 to inhibit Ca2+ mobilization but catalase had no effect.This suggests that the effects of SIN-1 on platelet Ca2+ handling resemble those of NO, but are modulated by simultaneous O2− release, independently of H2O2 formation.

Periodic interactions of GH-releasing factor and somatostatin can augment GH release in vitro

1987 ◽  
Vol 253 (5) ◽  
pp. E508-E514
Author(s):  
J. Weiss ◽  
M. J. Cronin ◽  
M. O. Thorner
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Male Rat ◽  
Base Line ◽  
Additive Effects ◽  
Growth Hormone Releasing Factor ◽  
The Impact

Growth hormone (GH) is secreted as pulses in vivo. To understand the signals governing this periodicity, we have established a perifusion-based model of pulsatile GH release. Male rat anterior pituitaries were dispersed and perifused with pulses of human growth hormone-releasing factor-(1--40) (GHRF), with or without a continuous or discontinuous somatostatin tonus. An experiment was composed of a 1-h base-line collection followed by four 3-h cycles; each contained single or paired 10-min infusion(s) of 3 nM GHRF. In testing the impact of somatostatin, the protocol was identical except that 0.3 nM somatostatin was added 30 min into the base-line period and then was either continued throughout the study or withdrawn during the periods of GHRF infusion. GH base lines with somatostatin were lower than vehicle base lines (P less than 0.05). GHRF pulses generated consistent peaks of GH release between 200 and 300 ng. min-1. (10(7) cells)-1, and these peaks were not altered by continuous somatostatin. In contrast, withdrawal of somatostatin during GHRF administration elicited markedly higher GH peaks (P less than 0.05) and more total GH release (P less than 0.05). This response could not be accounted for by the additive effects of GHRF and somatostatin withdrawal.

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