Relation between cholinergic and histaminergic components in reflex vasodilatation in the dog

1978 ◽  
Vol 234 (3) ◽  
pp. H305-H311 ◽  
Author(s):  
F. Rengo ◽  
B. Trimarco ◽  
M. Chiariello ◽  
L. Sacca ◽  
R. Violini ◽  
...  
Keyword(s):  
Histamine Release ◽  
Intravenous Injection ◽  
Cholinergic System ◽  
Perfusion Pressure ◽  
Gracilis Muscle ◽  
Systemic Hypertension ◽  
Receptor Blockade ◽  
Acetyl Choline ◽  
Baroreceptor Stimulation ◽  
Stimulation Of

Previous studies have shown that phentolamine is able to reverse the reflex vasodilatation produced by transitory baroreceptor stimulation by blocking sympathetic, histaminergic, and cholinergic components. A direct anticholinergic action of phentolamine has never been described; however, since it is known that this drug is capable of inhibiting histamine release during the reflex vasodilatation, it is possible that its ability to block the cholinergic component of the reflex is related to the latter property. Therefore, this study was undertaken in an attempt to identify possible relationships between cholinergic and histaminergic components of the reflex vasodilatation. Accordingly, in mongrel dogs the gracilis muscle was isolated and perfused and then loaded with 14C-labeled histamine. A transitory systemic hypertension was induced by intravenous injection of norepinephrine; this produced a reflex vasodilatation, shown by the fall in perfusion pressure, which was accompanied by an increase of histamine release from the muscle. Vagal block induced by atropine pretreatment reduced the fall in perfusion pressure induced by the systemic hypertension and produced a reduction of histamine release during the vasodilatation. In another group of animals a vasodilatation in the perfused muscle was induced by injection of acetylcholine. This response was accompanied by an increase in histamine release from the gracilis muscle. Alpha-receptor blockade, which has been shown to inhibit histamine release, reduced this acetyl-choline-induced vasodilatation. These results, while confirming the participation of the cholinergic system in the reflex vasodilatation elicited by transitory stimulation of the arterial baroreceptors, seem to demonstrate that this component is mediated almost exclusively by histamine release.

CATECHOLAMINE ANTAGONISM TO OXYTOCIN-INDUCED MILK-EJECTION

1971 ◽  
Vol 68 (1_Suppla) ◽  
pp. S5-S38 ◽  
Author(s):  
Helmuth Vorherr
Keyword(s):  
Receptor Blockade ◽  
Milk Ejection ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Beta Receptors ◽  
Alpha Receptors ◽  
Adrenergic Blockers ◽  
Beta Receptor Blockade ◽  
Second Pain ◽  
Stimulation Of

ABSTRACT In lactating rats and rabbits the mode of antagonism of sympathomimetics, angiotensin or pain toward oxytocin-induced milk-ejection was investigated. In rats intra-arterial (intrafemoral) doses of 0.01–0.02 μg or intravenous (iv) doses of 0.1–0.5 μg of either epinephrine, isoproterenol, norepinephrine, angiotensin or 10 μg of phenylephrine injected simultaneously with, or 30 seconds before an oxytocin dose (10 μU intrafemoral, 300 μU iv) greatly inhibited or suppressed the oxytocin response. A 15 second pain stimulus caused moderate inhibition. With alpha-receptor blockade pain, epinephrine, isoproterenol, norepinephrine, phenylephrine and angiotensin inhibition were, respectively, 70%, 75%, 100%, 40%, 0% and 100%. Under beta-receptor blockade the corresponding values were 14%, 40%, 0%, 70%, 100% and 100%; with simultaneous intrafemoral injections neither catecholamine was inhibitory toward oxytocin. In corresponding rabbit experiments approximately 10-fold higher iv drug dosages were applied and similar results were observed. In both species, combined alpha and beta-receptor blockade nearly eliminated the antagonistic actions of sympathomimetics toward oxytocin, whereas angiotensin inhibition persisted unchanged. The results indicate: 1) Mammary myoepithelial cells contain beta-adrenergic receptors but no alpha-receptors; 2) Inhibition of oxytocin-induced milk-ejection by isoproterenol and phenylephrine is meditated through stimulation of myoepithelial beta-receptors (myoepithelial relaxation) and vascular alpha-receptors (vasoconstriction), respectively; 3) Epinephrine and norepinephrine inhibition of milk-ejection is due to stimulation of vascular alpha-receptors and myoepithelial beta-receptors; 4) Angiotensin effects are unrelated to adrenergic receptor mechanisms; 5) Administration of both alpha and beta-adrenergic blockers is desirable for stabilizing the sensitivity of the oxytocin milk-ejection assay preparation against interference from endogenous or exogenous catecholamines; 6) Other than using adrenergic blockers, pharmacologic doses of oxytocin can correct nursing difficulties in animals and man with hyperfunction of the adrenal-sympathetic system.

scholarly journals STUDIES ON THE EFFECT OF CERTAIN TOXIC SUBSTANCES IN BACTERIAL CULTURES ON THE MOVEMENT OF THE INTESTINES

1926 ◽  
Vol 43 (6) ◽  
pp. 785-795 ◽  
Author(s):  
E. E. Ecker ◽  
A. Rademaekers
Keyword(s):  
Intravenous Injection ◽  
Toxic Substances ◽  
Propulsive Efficiency ◽  
Spasmodic Contraction ◽  
Strong Stimulation ◽  
Small Intestines ◽  
Slight Rise ◽  
Longitudinal Muscles ◽  
Stimulation Of

Following intravenous injection, filtrates of young cultures of B. paratyphosus B often produce marked diarrhea in rabbits. A study was made of the effect of these toxic filtrates on the motility of the small intestines of the rabbit. The observations were made on a segment of the small intestines in situ, and in the living animal. It was found that an immediate slight rise of tone of the longitudinal muscles occurred following intravenous injection of sterile broth. The same rise was noted after the injection of the toxic filtrate; but with these it was followed later (10 minutes elapsing at least) by a very strong but gradual rise of the diastolic and systolic tone, i.e., by spasmodic contraction of the intestinal muscle, which persisted at times for as long as 2 hours. In order to record simultaneously the effect on the longitudinal and circular muscles, and the propulsive efficiency of the segment the Sollmann and Rademaekers modification of Baur's technique was employed. This arrangement showed that the stimulation of the longitudinal muscles is accompanied by a similarly strong stimulation of the circular muscles, by peristalsis, and therefore by a greatly increased propulsion of intestinal contents which was sufficient to overcome the inhibition that usually occurs after preparation of the animal. With this arrangement an instance of peristaltic spasm was also noted. Broth alone failed to produce the phenomenon. Isotonic magnesium chloride or sulfate added to the bath relaxed the muscles again. Animals under deep urethane anesthesia did not show the diarrhea occurring in the intact controls, but sometimes exhibited it after the effect of the anesthetic had disappeared. So far no effects have been observed on the isolated strip (Magnus method), and further studies are being made to localize the effect, to neutralize it with a specific antiserum, and to observe the effect of filtrates of other members of the bacterial group including the dysentery bacilli.

Intravenous injection of hypertonic NaCl solution stimulates pulmonary C-fibers in dogs

1991 ◽  
Vol 260 (5) ◽  
pp. H1522-H1530 ◽  
Author(s):  
T. E. Pisarri ◽  
A. Jonzon ◽  
H. M. Coleridge ◽  
J. C. Coleridge
Keyword(s):  
Intravenous Injection ◽  
Pulmonary Circulation ◽  
Bronchial Artery ◽  
Dependent Manner ◽  
Nacl Solution ◽  
Impulse Frequency ◽  
Minimum Effective Concentration ◽  
C Fibers ◽  
Hypertonic Solutions ◽  
Stimulation Of

Intravenous injection of hypertonic NaCl solution evokes reflex bradycardia and hypotension, effects thought to result from stimulation of afferent vagal endings in the lungs. To identify the afferents responsible for these effects, we recorded vagal impulses arising from endings in the lungs and lower airways of anesthetized dogs and examined the response to injection of hypertonic solutions into the pulmonary circulation. Injection of 4,800 mmol/l NaCl solution (1 ml/kg) stimulated 39 of 49 pulmonary C-fibers, their impulse frequency increasing 35-fold. Stimulation was concentration dependent, the minimum effective concentration being between 1,200 and 4,800 mmol/l. Rapidly adapting receptors were also stimulated in a concentration-dependent manner, 35 of 41 receptors being stimulated by 4,800 mmol/l NaCl solution, firing increasing fivefold. Bronchial C-fibers were not stimulated by injection into the pulmonary circulation but were by injection into the bronchial artery. Hypertonic urea solutions had qualitatively similar but smaller effects on pulmonary C-fibers and rapidly adapting receptors. The results suggest that the reflex effects of intravenous injection of hypertonic solutions result principally from stimulation of pulmonary C-fibers.

Characteristics and origin of myogenic response in isolated gracilis muscle arterioles

1994 ◽  
Vol 266 (3) ◽  
pp. H1177-H1183 ◽  
Author(s):  
D. Sun ◽  
G. Kaley ◽  
A. Koller
Keyword(s):  
Pressure Range ◽  
Perfusion Pressure ◽  
Gracilis Muscle ◽  
Tetraacetic Acid ◽  
Flow Conditions ◽  
Third Order ◽  
Before And After ◽  
Physiological Pressure ◽  
Arteriolar Diameter ◽  
Intravascular Pressure

Responses to changes in intravascular pressure of isolated rat gracilis muscle arterioles were investigated under no-flow conditions. First-, second-, and third- order arterioles were isolated and cannulated. Vascular diameters were measured with an image-shearing device and then recorded. In response to the step increases in perfusion pressure (from 20 to 160 mmHg, by 10- or 20-mmHg steps) arterioles constricted and developed active tone. For example, at 100, 80, and 50 mmHg pressure the steady-state active diameters of 1st-, 2nd-, and 3rd-order arterioles were 76.9 +/- 1.6, 32.3 +/- 1.1 and 22.3 +/- 3.2 microns, respectively. At the same perfusion pressure, by use of a Ca(2+)-free solution (ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid; 1 mM) containing sodium nitroprusside (SNP; 10(-4) M), the passive diameters (PD) of these vessels were 161.8 +/- 3.2, 76.0 +/- 1.7, and 47.6 +/- 2.2 microns. The negative slopes of the pressure-diameter curves indicate that in the physiological pressure range an inverse relationship exists between the arteriolar diameter and intravascular pressure. The maximum constriction expressed as a percent of PD was similar in the various sized arterioles (approximately 60%) but was reached at lower pressures in the smaller vessels. The vasoactive function of endothelium and vascular smooth muscle was assessed by the responses of arterioles to acetylcholine (ACh; 10(-6) M) and SNP (5 x 10(-8) M) before and after removal of the endothelium with air. After removal of the endothelium, dilation to ACh was abolished while dilation to SNP was retained.(ABSTRACT TRUNCATED AT 250 WORDS)

Release of nitric oxide and prostaglandin H2 to acetylcholine in skeletal muscle venules

1997 ◽  
Vol 272 (6) ◽  
pp. H2541-H2546 ◽  
Author(s):  
G. Dornyei ◽  
G. Kaley ◽  
A. Koller
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Perfusion Pressure ◽  
Thromboxane A2 ◽  
No Synthase ◽  
Gracilis Muscle ◽  
Vasoactive Agents ◽  
Before And After ◽  
Higher Doses

The role of endothelium in regulating venular resistance is not well characterized. Thus we aimed to elucidate the endothelium-derived factors involved in the mediation of responses of rat gracilis muscle venules to acetylcholine (ACh) and other vasoactive agents. Changes in diameter of perfusion pressure (7.5 mmHg)- and norepinephrine (10(-6) M)-constricted venules (approximately 225 microns in diam) to cumulative doses of ACh (10(-9) to 10(-4) M) and sodium nitroprusside (SNP, 10(-9) to 10(-4) M), before and after endothelium removal or application of various inhibitors, were measured. Lower doses of ACh elicited dilations (up to 42.1 +/- 4.7%), whereas higher doses of ACh resulted in smaller dilations or even constrictions. Endothelium removal abolished both ACh-induced dilation and constriction. In the presence of indomethacin (2.8 x 10(-5) M), a cyclooxygenase blocker, or SQ-29548 (10(-6) M), a thromboxane A2-prostaglandin H2 (PGH2) receptor antagonist, higher doses of ACh caused further dilation (up to 72.7 +/- 7%) instead of constriction. Similarly, lower doses of arachidonic acid (10(-9) to 10(-6) M) elicited dilations that were diminished at higher doses. These reduced responses were, however, reversed to substantial dilation by SQ-29548. The nitric oxide (NO) synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), significantly reduced the dilation to ACh (from 30.6 +/- 5.5 to 5.4 +/- 1.4% at 10(-6) M ACh). In contrast, L-NNA did not affect dilation to SNP. Thus ACh elicits the release of both NO and PGH2 from the venular endothelium.

Inhibition of Histamine Release in Experimental Diabetes

1957 ◽  
Vol 191 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Andres Goth ◽  
W. L. Nash ◽  
Mary Nagler ◽  
James Holman
Keyword(s):  
Histamine Release ◽  
Intravenous Injection ◽  
Experimental Diabetes ◽  
Egg White ◽  
Diabetic Rats ◽  
Plasma Histamine ◽  
Elevated Plasma ◽  
Edema Formation

Alloxan diabetic rats failed to show the characteristic edema and elevated plasma histamine levels which follow the intravenous injection of dextran or egg white. Pretreatment with insulin restored the ability of these rats to respond in a normal fashion. Insulin in normal rats promotes edema formation and histamine release induced by dextran or egg white. In contrast to these findings, neither diabetes nor insulin pretreatment exerted an influence on the response of rats to intravenously injected compound 48/80. These results suggest a hitherto unrecognized role of insulin in certain types of inflammation and histamine release.

Selective ETA vs. dual ETA/B receptor blockade for the prevention of sunitinib-induced hypertension and albuminuria in WKY rats

2019 ◽  
Vol 116 (10) ◽  
pp. 1779-1790 ◽  
Author(s):  
Katrina M Mirabito Colafella ◽  
Karla B Neves ◽  
Augusto C Montezano ◽  
Ingrid M Garrelds ◽  
Richard van Veghel ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Renal Injury ◽  
Angiogenesis Inhibitor ◽  
Receptor Blockade ◽  
Receptor Antagonism ◽  
Sunitinib Treatment ◽  
Wky Rats ◽  
Induced Hypertension ◽  
Eta Receptor ◽  
Stimulation Of

Abstract Aims Although effective in preventing tumour growth, angiogenesis inhibitors cause off-target effects including cardiovascular toxicity and renal injury, most likely via endothelin (ET)-1 up-regulation. ET-1 via stimulation of the ETA receptor has pro-hypertensive actions whereas stimulation of the ETB receptor can elicit both pro- or anti-hypertensive effects. In this study, our aim was to determine the efficacy of selective ETA vs. dual ETA/B receptor blockade for the prevention of angiogenesis inhibitor-induced hypertension and albuminuria. Methods and results Male Wistar Kyoto (WKY) rats were treated with vehicle, sunitinib (angiogenesis inhibitor; 14 mg/kg/day) alone or in combination with macitentan (ETA/B receptor antagonist; 30 mg/kg/day) or sitaxentan (selective ETA receptor antagonist; 30 or 100 mg/kg/day) for 8 days. Compared with vehicle, sunitinib treatment caused a rapid and sustained increase in mean arterial pressure of ∼25 mmHg. Co-treatment with macitentan or sitaxentan abolished the pressor response to sunitinib. Sunitinib did not induce endothelial dysfunction. However, it was associated with increased aortic, mesenteric, and renal oxidative stress, an effect that was absent in mesenteric arteries of the macitentan and sitaxentan co-treated groups. Albuminuria was greater in the sunitinib- than vehicle-treated group. Co-treatment with sitaxentan, but not macitentan, prevented this increase in albuminuria. Sunitinib treatment increased circulating and urinary prostacyclin levels and had no effect on thromboxane levels. These increases in prostacyclin were blunted by co-treatment with sitaxentan. Conclusions Our results demonstrate that both selective ETA and dual ETA/B receptor antagonism prevents sunitinib-induced hypertension, whereas sunitinib-induced albuminuria was only prevented by selective ETA receptor antagonism. In addition, our results uncover a role for prostacyclin in the development of these effects. In conclusion, selective ETA receptor antagonism is sufficient for the prevention of sunitinib-induced hypertension and renal injury.

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