Effects of Bradykinin on Pial Arteries and Arterioles in vitro and in situ

The effect of bradykinin on cerebrovascular resistance vessels was investigated by the use of in vitro and in situ preparations. Bradykinin, in the range of 10−10 to 10−5 M, elicited a concentration-dependent vasodilatation on both feline and human pial arteries in vitro; the half-maximal response was found to be approximately at 2.8 × 10−7 M and 1.3 × 10−8 M (EC50), respectively. This dilatatory effect of bradykinin in vitro was found only in arteries preconstricted with prostaglandin F2α or 5-hydroxytryptamine. In order to determine the effects of bradykinin on the diameter of cat pial arteries in situ, perivascular microapplication was employed. The dose-response curves obtained showed vasodilatation; the EC50 and the maximal response (EAm) were 4.4 × 10−7 M and 45.5% at 10−5 M, respectively. Statistically significant (p < 0.01) reactions were observed at 10−7 M and higher concentrations of bradykinin. The observed effects were independent of initial vessel size (80–260 μm). These in situ findings are very similar to those found in vitro. The isolated guinea pig ileum was used to check the stability of the bradykinin solutions. In this instance, a concentration-dependent contraction was found when “freshly prepared” or “5 hours stored” bradykinin was applied, indicating no measurable degradation of bradykinin. We conclude that bradykinin is a powerful vasodilator of both human and feline pial arteries.

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Effects of Enkephalins, Morphine, and Naloxone on Pial Arteries during Perivascular Microapplication

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1985.61 ◽

1985 ◽

Vol 5 (3) ◽

pp. 451-457 ◽

Cited By ~ 22

Author(s):

Michael Wahl

Keyword(s):

Partial Agonist ◽

Opiate Receptor ◽

Response Curves ◽

Pial Arteries ◽

Vascular Effect ◽

Cerebrovascular Resistance ◽

Agonist Action ◽

Resistance Vessels ◽

Television Image

The effects of the opiate receptor agonists, enkephalins and morphine, and the antagonist, naloxone, on cerebrovascular resistance vessels was investigated in situ by employing perivascular microapplication. Feline pial arteries with a resting diameter of 66–294 μm were tested. Vascular diameter was measured using television image splitting. Concentration-response curves revealed no change of diameter when Leu-enkephalin, d-Ala2-Leu-enkephalinamide, d-Ala2-Met-enkephalinamide, and morphine were applied in concentrations of 10−11–10−5 M. Considering the concentrations of enkephalins that have been found in natural cerebrospinal fluid or that can be expected in the vicinity of enkephalinergic synapses, the data obtained with the lower concentrations indicate that enkephalins are probably not important for the regulation of pial arterial resistance. At 10−4 M only the dilatation (4.3%) elicited by d-Ala2-Leu-enkephalinamide was statistically significant (p < 0.01). All four agonists at 10−3 M induced significant dilatations varying between 5.4 and 13.6%. Naloxone exerted no vascular effect per se at 10−5 and 10−4 M but a dilatation of 15.3% at 10−3 M. The latter can be explained by a partial agonist action. During simultaneous administration, naloxone (10−4 M) reduced the dilatations induced by 10−4 and 10−3 M d-Ala2-Leu-enkephalinamide dose dependently. This indicates that μ-and δ-opioid receptors, probably located at the vascular smooth muscle cell, were involved in the mediation of the dilatation induced by the highest concentrations of the compounds.

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Mechanisms of airway hypercontractility in basenji-greyhound dogs

Journal of Applied Physiology ◽

10.1152/jappl.1987.63.5.2008 ◽

1987 ◽

Vol 63 (5) ◽

pp. 2008-2014 ◽

Cited By ~ 1

Author(s):

T. M. Murphy ◽

N. M. Munoz ◽

C. A. Hirshman ◽

J. S. Blake ◽

A. R. Leff

Keyword(s):

Maximal Response ◽

Adrenergic Blockade ◽

Vagus Nerves ◽

Response Curves ◽

Bronchial Smooth Muscle ◽

Muscarinic Response ◽

Contractile Forces ◽

Stimulation Of

The comparative effects of contractile agonists and physiological stimulation of the tracheal and bronchial smooth muscle (BSM) response were studied isometrically in situ in five Basenji-greyhound (BG) and six mongrel dogs. Frequency-response curves generated by bilateral stimulation of the vagus nerves (0–20 Hz, 15–20 V, 2-ms duration) elicited greater maximal contraction in mongrel trachea (36.8 +/- 8.1 vs. 26.9 +/- 4.0 g/cm; P less than 0.02) and exhibited greater responsiveness in mongrel BSM (half-maximal response to electrical stimulation 3.0 +/- 1.1 vs. 7.0 +/- 0.5 Hz; P less than 0.05) compared with BG dogs. However, muscarinic sensitivity to intravenous methacholine (MCh) was substantially greater in BG dogs; MCh caused contraction greater than 1.5 g/cm at a mean dose of 3.0 X 10(-10) mol/kg for BG dogs compared with 5.1 X 10(-9) mol/kg for mongrel controls (P less than 0.03, Mann-Whitney rank-sum test). In contrast to the muscarinic response, the contractile response elicited by intravenous norepinephrine after beta-adrenergic blockade was similar in trachea and bronchus for both mongrel and BG dogs. Our data confirm previous in vitro demonstration of tracheal hyporesponsiveness in BG dogs and demonstrate that the contraction resulting from efferent parasympathetic stimulation is less in the BG than mongrel dogs. However, postsynaptic muscarinic responsiveness of BG BSM is substantially increased. We conclude that a component of airway responsiveness in BG dogs depends directly on contractile forces generated postsynaptically that are nongeometry dependent, postjunctional, and agonist specific.

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Expression of airway contractile properties and acetylcholinesterase activity in swine

Journal of Applied Physiology ◽

10.1152/jappl.1989.67.1.174 ◽

1989 ◽

Vol 67 (1) ◽

pp. 174-180 ◽

Cited By ~ 30

Author(s):

T. M. Murphy ◽

R. W. Mitchell ◽

J. S. Blake ◽

M. M. Mack ◽

E. A. Kelly ◽

...

Keyword(s):

Smooth Muscle ◽

Acetylcholinesterase Activity ◽

Contractile Properties ◽

Tracheal Smooth Muscle ◽

Cholinesterase Inhibition ◽

Maximal Response ◽

Response Curves ◽

Cross Sectional

We studied the effect of maturation on contractile properties of tracheal smooth muscle from seventeen 2-wk-old swine (2ws) and fifteen 10-wk-old swine (10ws) in situ and in vitro. The response to parasympathetic stimulation was studied in situ in isometrically fixed segments. Contraction was elicited at lower frequencies [half-maximal response to electrical stimulation (ES50) = 6.7 +/- 0.05 Hz] in 2ws than in 10ws (ES50 = 9.1 +/- 0.4 Hz; P less than 0.01). Despite substantial differences in morphometrically normalized cross-sectional area in 2ws (0.012 +/- 0.003 cm2) and 10ws (0.028 +/- 0.001 cm2; P less than 0.01), maximal active tension elicited by parasympathetic stimulation was similar (12.4 +/- 3.2 g/cm in 2ws vs. 13.3 +/- 2.3 g/cm in 10ws; P = NS). In separate in vitro studies in 25 tracheal smooth muscle strips from 10 swine, concentration-response curves generated with potassium-substituted Krebs solution (KCl) were similar in 2ws and 10ws. In 58 other strips (10 swine), maximal active force elicited with acetylcholine (ACh) in 2ws was significantly greater than for 10ws (P less than 0.001). Removal of the epithelium had no effect. However, cholinesterase inhibition with 10(-7) M physostigmine augmented the response to ACh in 10ws (P less than 0.02) but not 2ws. We demonstrate increased force generation and sensitivity to vagal stimulation in 2ws vs. 10ws, which corresponds to increased reactivity to ACh in vitro. The relative hyperresponsiveness in 2ws is specific for cholinergic response and is attenuated at least in part by maturation of the activity of acetylcholinesterase enzyme.

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Effects of Kininase II Inhibitors on the Vasomotor Response to Bradykinin of Feline Intracranial and Extracranial Arteries in vitro and in situ

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1983.49 ◽

1983 ◽

Vol 3 (3) ◽

pp. 339-345 ◽

Cited By ~ 18

Author(s):

Michael Wahl ◽

Alan R. Young ◽

Lars Edvinsson ◽

Franz Wagner

Keyword(s):

Cerebral Arteries ◽

Surrounding Tissue ◽

Experimental Conditions ◽

Pial Arteries ◽

Simultaneous Application ◽

Kininase Ii ◽

Middle Cerebral Arteries ◽

Prostaglandin F

Bradykinin is known to effect a vasodilatation of feline cerebral arteries in situ and of both human and feline pial arteries in vitro. In order to demonstrate whether kininase II (localized within the vessel wall or in the surrounding tissue or fluid) influences the response to bradykinin, two different inhibitors of this bradykinin degradation enzyme were tested. Perivascular microapplication of potentiator C (10−10–10−4 M) or captopril (10−10–10−3 M) did not, by itself, change the diameter of feline pial arteries (87–305 μm) in situ. In a similar investigation, the dilating action of bradykinin (10−8–10−5 M) was not modified by the simultaneous application of potentiator C or captopril (10−5 M). Furthermore, the relaxing effect of bradykinin (10−10–10−4 M) on isolated feline middle cerebral arteries (preconstricted with 5-hydroxytryptamine or prostaglandin F2α) was not influenced by the presence of captopril (10−7 M). In contrast, when studied on isolated extracranial vessel segments (feline sublingual artery), bradykinin caused a concentration-dependent constriction of the artery. This constriction was completely reversed to dilatation in the presence of captopril (10−7 M). Moreover, the characteristic effect of kininase II inhibition was demonstrated in the isolated guinea pig ileum preparation. In this instance, bradykinin induced a concentration-dependent contraction that was enhanced by potentiator C or captopril. We conclude, therefore, that bradykinin exerts variable responses on vascular smooth muscle, depending on the species used, the muscle location and experimental conditions. Finally, the in situ and in vitro findings for pial and middle cerebral arteries demonstrate that kininase II does not modify the dilating effect of bradykinin under our experimental conditions.

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Altered contractility of circular and longitudinal muscle in TNBS-inflamed guinea pig ileum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.272.5.g1258 ◽

1997 ◽

Vol 272 (5) ◽

pp. G1258-G1267 ◽

Cited By ~ 9

Author(s):

J. P. Martinolle ◽

R. Garcia-Villar ◽

J. Fioramonti ◽

L. Bueno

Keyword(s):

Guinea Pig ◽

Dose Range ◽

Circular Muscle ◽

Maximal Response ◽

Guinea Pig Ileum ◽

Trinitrobenzenesulfonic Acid ◽

Response Curves ◽

Contractile Responses ◽

Guinea Pig Model

Intestinal motility disorders are often associated with gut inflammation. We evaluated, in vitro under isometric conditions, changes in contractility of longitudinal and circular muscle layers from guinea pig ileum after 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis. TNBS treatment did not modify length-active tension relationships for both muscle layers, whereas a significant increase in passive tension was observed in the circular muscle response to stretching. Moreover, in both control and inflamed strips at optimal stretch, concentration-response curves to KCl were similar for both layers. In contrast, contractile responses to receptor agonists were differentially altered in both layers in comparison with controls. Thus, in longitudinal strips from TNBS-treated ileum, there was a twofold increase in maximal response (Emax) induced by carbachol and histamine without modification of 50% effective concentration (EC50) values; responses to 5-hydroxytryptamine (5-HT) were not modified; both alpha 1- and alpha 2-adrenoceptor-mediated responses to epinephrine were abolished. In circular strips, inflammation did not affect the Emax induced by carbachol and histamine but led to increased EC50 values; Emax to 5-HT was reduced without change in EC50 values. Moreover, in the dose range used (0.1 nM to 0.1 mM), a maximal response to carbachol was not obtained in inflamed circular strips. The results indicate that in the guinea pig model of TNBS-induced ileitis, the in vitro contractile responses of circular and longitudinal smooth muscle to the stimulation of various receptors are differentially altered, whereas non-receptor-mediated contraction to KCl depolarization is not modified.

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Effect of insulin on glucose metabolism in adipocytes from virgin and late-pregnant rats

Biochemical Journal ◽

10.1042/bj2240685 ◽

1984 ◽

Vol 224 (2) ◽

pp. 685-688 ◽

Cited By ~ 10

Author(s):

A Leturque ◽

M Guerre-Millo ◽

M Lavau ◽

J Girard

Keyword(s):

Glucose Metabolism ◽

High Sensitivity ◽

Late Pregnancy ◽

Maximal Response ◽

Maximal Effect ◽

Insulin Stimulation ◽

Response Curves ◽

Pregnant Rats

Under basal conditions (zero insulin), paraovarian adipocytes from 19-day-pregnant rats exhibited the same rates of [U-14C]glucose conversion into CO2 and total lipids as did those from age-matched virgin rats. The dose-response curves for insulin stimulation of glucose metabolism were similar in both groups: maximal response (+100% over basal values) and high sensitivity (half-maximal effect at 0.05 nM-insulin). The present results suggest that the insulin resistance in vivo that occurs during late pregnancy may involve circulating factors lost in vitro.

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Direct Vascular Effects of Agents Used in the Pharmacotherapy of Cerebrovascular Disease on Isolated Cerebral Vessels

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1981.12 ◽

1981 ◽

Vol 1 (1) ◽

pp. 117-128 ◽

Cited By ~ 20

Author(s):

Alan R. Young ◽

Michele Bouloy ◽

Jean-François Boussard ◽

Lars Edvinsson ◽

Eric T. MacKenzie

Keyword(s):

Metabolic Disease ◽

Maximal Response ◽

Vascular Effects ◽

Pial Arteries ◽

Xanthine Derivatives ◽

Pial Vessels ◽

Agonist Concentration ◽

The Mean ◽

Methyl Xanthine

The direct vasomotor effects of a number of agents used in the therapy of cerebral circulatory and metabolic disease were studied in isolated segments of cat pial vessels in vitro. Studies were repeated eight times generally, thus permitting the calculation of the mean maximum response—termed EAm (in dynes)—and of the molar agonist concentration required to effect the half-maximal response, termed EC50. The results obtained with various agonists were compared to a well-documented vasodilator, acetylcholine ( EAm = −780 dyn; EC50 = 0,029 μm) and a known vasoconstrictor, 5-hydroxytryptamine ( EAm = + 1630 dyn; EC50 = 0.036 μm). Papaverine and its derivatives effected a relaxation of the pial arteries with the following order of potency: YC-93 > papaverine > naftidrofuryl > viquidil. The EC50 for papaverine was 1,5 μm. Methyl xanthine derivatives (aminophylline, pentoxifylline, and theophylline) were essentially inactive, In contrast, drugs that are known to be capable of decreasing the volume of an experimental infarction, many of which are described as α-adrenolytic agents, contracted the isolated cerebrovascular smooth muscle, Their order of efficacy, based on the mean EAm values, was ifenprodil > vincamine > nicergoline > dihydroergotoxine > raubasine, In addition, it was considered worthwhile to determine whether the ifenprodil-induced vasoconstriction occurred when human, rather than cat, pial vessels were studied, Ifenprodil and vincamine contracted the human vessels in a biphasic manner; the EC50 was calculated to be 2,0 and 30 μm. Based on the above observations, the following comments would appear justified, Firstly, an increase in cerebral blood flow does not necessarily mean a compound is a direct vasodilator. Secondly, the vasoconstrictory actions of some agents correlate well with their anti-ischaemic properties (e.g., ifenprodil, vincamine, and nicergoline), Lastly, one action of effective anti-ischaemic agents might be to reduce flow, by vasoconstriction, in hyperaemic tissue: the inverse “steal” effect.

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Arg-Vasotocin Directly Activates Isotocin Receptors and Induces COX2 Expression in Ovoviviparous Guppies

Frontiers in Endocrinology ◽

10.3389/fendo.2021.617580 ◽

2021 ◽

Vol 12 ◽

Author(s):

Li Kang Lyu ◽

Jian Shuang Li ◽

Xiao Jie Wang ◽

Yi Jia Yao ◽

Ji Fang Li ◽

...

Keyword(s):

Poecilia Reticulata ◽

Intraperitoneal Administration ◽

Gene Expression Measurement ◽

Reproductive Behaviors ◽

Prostaglandin F ◽

Rate Limiting ◽

Cox2 Expression ◽

Expression Measurement

Oxytocin (OT) is a crucial regulator of reproductive behaviors, including parturition in mammals. Arg-vasopressin (AVP) is a nonapeptide homologous to Arg-vasotocin (AVT) in teleosts that has comparable affinity for the OT receptor. In the present study, ovoviviparous guppies (Poecilia reticulata) were used to study the effect of AVT on delivery mediated by the activation of prostaglandin (PG) biosynthesis via isotocin (IT) receptors (ITRs). One copy each of it and avt and two copies of itrs were identified in guppies. The results of the affinity assay showed that various concentrations of AVT and IT (10−6, 10−7, and 10−8 mol/L) significantly activated itr1 (P < 0.05). In vitro experiments revealed significant upregulation (P < 0.05) of cyclooxygenase 2 (cox2), which is the rate-limiting enzyme involved in PG biosynthesis, and itr1 by AVT and IT. Furthermore, dual in situ hybridization detected positive signals for itr1 and cox2 at the same site, implying that ITR1 may regulate cox2 gene expression. Measurement of prostaglandin F2a (PGF2a) concentrations showed that AVT induced PGF2a synthesis (P < 0.05) and that the effect of IT was not significant. Finally, intraperitoneal administration of PGF2a significantly induced premature parturition of guppies. This study is the first to identify and characterize AVT and ITRs in guppies. The findings suggest that AVT promotes PG biosynthesis via ITR and that PGF2a induces delivery behavior in ovoviviparous guppies.

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