Abstract 15585: Sex Dimorphism in Prostaglandins’ Role in Thromboxane-dependent Contraction in the Rat Middle Cerebral Artery

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Victor M Pulgar ◽  
Ibrahim Elsaangeedy ◽  
Liliya M Yamaleyeva
Keyword(s):  
Ex Vivo ◽  
Cerebral Arteries ◽  
Cerebrovascular Reactivity ◽  
Maximal Response ◽  
Hormonal Changes ◽  
Sprague Dawley ◽  
Maximal Contraction ◽  
Response Curves ◽  
Sprague Dawley Rats ◽  
Pre Treatment

Introduction: Recent evidences suggest that sex and estrogen can influence cerebrovascular reactivity. We investigated the role of prostanoids and the estrogen receptor (ER) ex vivo in isolated middle cerebral arteries from male (M-MCA) and female (F-MCA) rats. Methods: MCA segments isolated from 20-week-old male and female Sprague-Dawley rats were mounted on a wire Multi Myograph (DMT) to measure isometric tone. Acetylcholine (ACh) was used to assess endothelium integrity. Concentration response curves to the thromboxane analog U46619 (U4, 10 -11 -10 -5 M) were performed in arteries intact or pre-treated with indomethacin (I,10 -5 M) or the ER antagonist G15 (G, 10 -6 M). Data were acquired with Powerlab 8 (ADInstruments) and recorded with LabChart v8 (ADInstruments). Response to K + was expressed in mN/mm whereas U4 maximal contraction as percent of maximal response to 75mM K + (%K MAX ) and sensitivity as pD 2 (-LogEC 50 ). Results: M-MCA (n=10) and F-MCA (n=13) displayed similar optimal diameters (M vs. F; 214±12 vs. 218±5 μm, p>0.05) and ACh-dependent relaxation (M vs. F; 71±11 vs. 78±10 % pre-constricted tone; 7.3±0.4 vs. 7.2±0.2, p>0.05). A greater contraction to K + was observed in M-MCA (M vs. F; 1±0.2 vs. 0.6±0.1 mN/mm, p<0.05). M- and F-MCA showed similar maximal contraction (M vs. F; 116±6 vs. 109±10 %K MAX ) and sensitivity (M vs. F; 7.2±0.2 vs. 7.3±0.2) to U4. Pre-incubation with Indomethacin lowered maximal response and sensitivity (M vs. M-I; 116±6 vs. 97±5%K MAX, p<0.05; 7.2±0.2 vs. 6.8±0.1, p<0.05) to U4 in M-MCA, with no effect on F-MCA (F vs. F-I; 109±9 vs. 113±7%K MAX ; 7.3±0.2 vs. 7.3±0.2). Pre-treatment with G15 increased U4 sensitivity in M-MCA (M vs. M-G; 7.3±0.2 vs. 7.8±0.2, p<0.05), with no effect in F-MCA (F vs. F-G; 7.3±0.2 vs. 7.4±0.3). Conclusions: Our data demonstrate sex differences in thromboxane-dependent contraction of MCA in middle-aged rats. Hormonal changes during the estrous cycle may contribute to a greater variability of F-MCA responses.

scholarly journals EVALUATION OF ANTIDIARRHEAL ACTIVITY OF ETHANOLIC LEAF EXTRACT OF ERIOBOTRYA JAPONICA LINDL

2018 ◽  
Vol 11 (9) ◽  
pp. 502
Author(s):  
Davie Rexon Kamadyaapa ◽  
Mavuto Masopera Gondwe ◽  
Mathulo Shauli ◽  
Constance Sewani Rusike ◽  
Jehu Iputo
Keyword(s):  
Castor Oil ◽  
Leaf Extract ◽  
Eriobotrya Japonica ◽  
Cytotoxicity Test ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Adrenoceptor Blocker ◽  
Antidiarrheal Activity ◽  
Pre Treatment ◽  
Ethanolic Leaf Extract

Objective: The study was carried out to investigate the antidiarrheal activity of ethanolic leaf extract of Eriobotrya japonica (EEJ) using various models of experimental diarrhea.Methods: Antidiarrheal property of EEJ at 100, 200, and 400 mg/kg/bwt was evaluated using castor oil-induced diarrhea, castor oil-induced enteropooling, and gastrointestinal propulsive models of experimental diarrhea in Sprague Dawley rats of both sexes, weighing 200–250 g. Cytotoxicity test of EEJ was performed using brine shrimp bioassay.Results: Toxicity assay of EEJ showed a lethal concentration value of 1225 μg/ml suggesting non-toxicity. EEJ significantly (p<0.05) and dose-dependently (100, 200 and 400 mg/kg/bwt) inhibited castor oil-induced diarrhea by 38.1%, 76.19%, and 100%, respectively, and enteropooling by 28%, 56%, and 88%, respectively, compared with control. Pre-treatment with yohimbine, α2-adrenoceptor blocker significantly reversed the protective effect of EEJ (400 mg/kg) against castor oil-induced diarrhea and against castor oil-induced enteropooling, suggesting the involvement of α2-adrenoceptors in antidiarrheal property of EEJ. Furthermore, EEJ significantly (p<0.05) and dosedependently (100, 200, and 400 mg/Kg/bwt) inhibited gastrointestinal motility by 28%, 62%, and 83.92%, respectively.Conclusion: The study has demonstrated the antidiarrheal potential of ethanolic leaf extract of EEJ, which may be attributable to its dual antisecretory and antimotility activities probably through activation of the sympathetic α2-adrenergic pathway.

Time course of airway hyperresponsiveness and remodeling induced by hyperoxia in rats

1995 ◽  
Vol 269 (2) ◽  
pp. L227-L233 ◽  
Author(s):  
J. L. Szarek ◽  
H. L. Ramsay ◽  
A. Andringa ◽  
M. L. Miller
Keyword(s):  
Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Time Course ◽  
Electrical Field Stimulation ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Electrical Field ◽  
Muscle Area ◽  
Sprague Dawley Rats ◽  
The Relationship

The purpose of this study was to answer two questions concerning hyperoxia-induced airway hyperresponsiveness: 1) What is the time course of the development of airway hyperresponsiveness? 2) What is the relationship between the increase in responsiveness and smooth muscle area? Segments of intrapulmonary bronchi were isolated from male Sprague-Dawley rats that had been exposed to 80-85% O2 for a period of 1, 3, 5, or 7 days and from aged-matched control animals that breathed room air. Hyperoxia increased the sensitivity (log concentration or frequency that elicited a half-maximal response) and reactivity (maximum tension developed) of the airways to electrical field stimulation (EFS) after 3, 5, and 7 days; sensitivity to acetylcholine was not affected, but reactivity was increased after 7 days. Hyperoxia increased smooth muscle area beginning 5 days after commencing the exposure. After normalizing tension responses to smooth muscle area, reactivity of the airways to the stimuli was not different between the two groups, but sensitivity to EFS was still increased. The increase in reactivity observed after 5 and 7 days of exposure can be explained by an increase in smooth muscle area that occurred at these time points. The fact that the sensitivity of the airways to EFS remained increased after normalization, together with the fact that the increase in airway responsiveness after 3 days of exposure occurred at a time when smooth muscle area was not different from control, suggests that mechanisms other than increased smooth muscle area contribute to the development of hyperoxia-induced airway hyperresponsiveness.

Cerebral artery reactivity changes during pregnancy and the postpartum period: a role in eclampsia?

2004 ◽  
Vol 286 (6) ◽  
pp. H2127-H2132 ◽  
Author(s):  
Marilyn J. Cipolla ◽  
Lisa Vitullo ◽  
John McKinnon
Keyword(s):  
Cerebral Artery ◽  
Postpartum Period ◽  
Cerebral Arteries ◽  
Hypertensive Encephalopathy ◽  
Myogenic Tone ◽  
No Production ◽  
Sprague Dawley ◽  
Cerebrovascular Resistance ◽  
Sprague Dawley Rats ◽  
Myogenic Activity

Eclampsia is thought to be similar to hypertensive encephalopathy, whereby acute elevations in intravascular pressure cause forced dilatation (FD) of intrinsic myogenic tone of cerebral arteries and arterioles, decreased cerebrovascular resistance, and hyperperfusion. In the present study, we tested the hypothesis that pregnancy and/or the postpartum period predispose cerebral arteries to FD by diminishing pressure-induced myogenic activity. We compared the reactivity to pressure (myogenic activity) as well as factors that modulate the level of tone of third-order branches (<200 μm) of the posterior cerebral artery (PCA) that were isolated from nonpregnant (NP, n = 7), late-pregnant (LP, 19 days, n = 10), and postpartum (PP, 3 days, n = 8) Sprague-Dawley rats under pressurized conditions. PCAs from all groups of animals developed spontaneous tone within the myogenic pressure range (50–150 mmHg) and constricted arteries at 100 mmHg (NP, 30 ± 3; LP, 39 ± 4; and PP, 42 ± 7%; P > 0.05). This level of myogenic activity was maintained in the NP arteries at all pressures; however, both LP and PP arteries dilated at considerably lower pressures compared with NP, which lowered the pressure at which FD occurred from >175 for NP to 146 ± 6.5 mmHg for LP ( P < 0.01 vs. NP) and 162 ± 7.7 mmHg for PP ( P < 0.01 vs. NP). The amount of myogenic tone was also significantly diminished at 175 mmHg compared with NP: percent tone for NP, LP, and PP animals were 35 ± 2, 11 ± 3 ( P < 0.01 vs. NP), and 20 ± 7% ( P < 0.01 vs. NP), respectively. Inhibition of nitric oxide (NO) with 0.1 mM Nω-nitro-l-arginine (l-NNA) caused constriction of all vessel types that was significantly increased in the PP arteries, which demonstrates significant basal NO production. Reactivity to 5-hydroxytryptamine (serotonin) was assessed in the presence of l-NNA and indomethacin. There was a differential response to serotonin: PCAs from NP animals dilated, whereas LP and PP arteries constricted. These results suggest that both pregnancy and the postpartum period predispose the cerebral circulation to FD at lower pressures, a response that may lower cerebrovascular resistance and promote hyperperfusion when blood pressure is elevated, as occurs during eclampsia.

17β-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage

2007 ◽  
Vol 292 (1) ◽  
pp. H245-H250 ◽  
Author(s):  
Zheng F. Ba ◽  
Ailing Lu ◽  
Tomoharu Shimizu ◽  
László Szalay ◽  
Martin G. Schwacha ◽  
...  
Keyword(s):  
Control Level ◽  
No Synthase ◽  
Sprague Dawley ◽  
Response Curves ◽  
Endothelin 1 ◽  
Sprague Dawley Rats ◽  
17Β Estradiol ◽  
Synthase Inhibitor

Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17β-estradiol (E2) treatment following trauma-hemorrhage alters these ET-1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor (ER) subtypes (ER-α and ER-β) and the endothelium-localized downstream mechanisms of actions of E2 remain unclear. We hypothesized that E2 attenuates increased ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma-hemorrhage with or without E2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET-1 were determined, and the vasoactive properties of E2, propylpyrazole triol (PPT, ER-α agonist), and diarylpropionitrile (DPN, ER-β agonist) were determined. The results showed that trauma-hemorrhage significantly increased ET-1-induced vasoconstriction; however, administration of E2 normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the sham-operated control level. The ER-β agonist DPN counteracted ET-1-induced vasoconstriction, whereas the ER-α agonist PPT was ineffective. Moreover, the vasorelaxing effects of E2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide (NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E2. Thus, E2 administration attenuates ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway that is dependent on endothelium-derived NO synthesis.

Sexual dimorphism in vasopressin-induced contraction of rat aorta

1991 ◽  
Vol 260 (2) ◽  
pp. H453-H458 ◽  
Author(s):  
J. N. Stallone ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Estrous Cycle ◽  
Vascular Reactivity ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Female Rats ◽  
Male Rats ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Tension Development ◽  
Sprague Dawley Rats

Previously, we reported that, in the rat, pressor responsiveness to vasopressin (VP) is higher in males than in females during most phases of the estrous cycle. To explore the role of the vasculature in this phenomenon, we examined vascular reactivity to VP in thoracic aortas of male rats and female rats during each phase of the estrous cycle. Aortic rings were prepared from age-matched male and female Sprague-Dawley rats and mounted for isometric tension recording. Maximal response of female aortas to VP (4,246 +/- 163 mg/mg ring dry wt) was more than twice (P less than 0.001) that of male aortas (1,877 +/- 215 mg/mg ring wt). Sensitivity of female aortas to VP was substantially higher (P less than 0.001) than that of male aortas (EC50: 10.9 +/- 0.7 vs. 19.0 +/- 1.6 nM, respectively). Maximal rate of tension development (dT/dtmax) during contraction with VP was nearly twofold higher (P less than 0.01) in female aortas (536 +/- 23 mg/min) than in male aortas (300 +/- 19 mg/min). Maximal response, sensitivity, and dT/dtmax of female aortas did not vary significantly during the estrous cycle. Maximal response of female aortas to phenylephrine (PE; 1,251 +/- 93 mg/mg ring wt) was half that (P less than 0.001) of male aortas (2,546 +/- 194 mg/mg ring wt); sensitivity to PE did not differ significantly (EC50: 0.33 +/- 0.02 vs. 0.38 +/- 0.06 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Oxytocin resistance in Brattleboro rat adipocytes and comparative studies on insulin or oxytocin responsiveness in normal rat adipocytes

1983 ◽  
Vol 61 (11) ◽  
pp. 1418-1425 ◽  
Author(s):  
K. Hanif ◽  
H. J. Goren ◽  
R. M. Geonzon ◽  
K. Lederis ◽  
M. D. Hollenberg
Keyword(s):  
Calcium Concentration ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Assay Medium ◽  
Rat Adipocytes ◽  
Sprague Dawley Rats ◽  
Normal Rat ◽  
Increased Sensitivity ◽  
Long Evans ◽  
Treatment Use

We have evaluated factors, other than genetic, which might be related to the lack of an oxytocin-mediated insulinlike response (glucose oxidation; lipogenesis) in adipocytes from Brattleboro rats, homozygous for the diabetes insipidus trait (HoDI rats). The manoeuvres used in an attempt to restore the glucoregulatory responses to oxytocin in HoDI cells (increased glucose in the fat pad digestion medium; increased calcium concentration in the oxidation assay; estrogen treatment; use of [1-14C]glucose as substrate; inclusion of adenosine in the assay medium; vasopressin replacement therapy) uniformly failed to result in oxytocin activation of HoDI adipocytes, in contrast, the contractile responses of estrogenized HoDI rat uteri were indistinguishable from those of estrogenized normal rats. We conclude that the nonresponsiveness of the Brattleboro adipocytes to the glucoregulatory actions of oxytocin is not due to factors related to the conditions of the bioassay. On the other hand, in normal fat cells (from Sprague–Dawley and Long Evans rats), oxytocin responsiveness was augmented by a number of the manoeuvres mentioned above, most notably by the inclusion of either calcium (10 mM) or adenosine (10 μM) in the assay medium. Nonetheless, the maximum oxytocin responsiveness of adipocytes from Long Evans or Sprague–Dawley rats, under all conditions of assay, was still only a fraction (less than 20%) of the maximal response to insulin. The effect of adenosine on oxytocin action (increased sensitivity, without an effect on the maximum response) is in keeping with the previously observed effects of this nucleoside on the action of insulin; our results thus pointed to a new parallel in the action of insulin and oxytocin.

scholarly journals Vascular function in rats with adenine-induced chronic renal failure

2012 ◽  
Vol 302 (12) ◽  
pp. R1426-R1435 ◽  
Author(s):  
Lisa Nguy ◽  
Holger Nilsson ◽  
Jaana Lundgren ◽  
Maria E. Johansson ◽  
Tom Teerlink ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Vascular Function ◽  
Ex Vivo ◽  
Mesenteric Arteries ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Severe Renal Failure ◽  
Stress Markers

The aim of the present study was to characterize the function of resistance arteries, and the aorta, in rats with adenine-induced chronic renal failure (A-CRF). Sprague-Dawley rats were randomized to chow with or without adenine supplementation. After 6–10 wk, mesenteric arteries and thoracic aortas were analyzed ex vivo by wire myography. Plasma creatinine concentrations were elevated twofold at 2 wk, and eight-fold at the time of death in A-CRF animals. Ambulatory systolic and diastolic blood pressures measured by radiotelemetry were significantly elevated in A-CRF animals from week 3 and onward. At death, A-CRF animals had anemia, hyperphosphatemia, hyperparathyroidism, and elevated plasma levels of asymmetric dimethylarginine and oxidative stress markers. There were no significant differences between groups in the sensitivity, or maximal response, to ACh, sodium nitroprusside (SNP), norepinephrine, or phenylephrine in either mesenteric arteries or aortas. However, in A-CRF animals, the rate of aortic relaxation was significantly reduced following washout of KCl (both in intact and endothelium-denuded aorta) and in response to ACh and SNP. Also the rate of contraction in response to KCl was significantly reduced in A-CRF animals both in mesenteric arteries and aortas. The media of A-CRF aortas was thickened and showed focal areas of fragmented elastic lamellae and disorganized smooth muscle cells. No vascular calcifications could be detected. These results indicate that severe renal failure for a duration of less than 10 wk in this model primarily affects the aorta and mainly slows the rate of relaxation.

Contribution of whole blood to the control of plasma asymmetrical dimethylarginine

2006 ◽  
Vol 291 (4) ◽  
pp. H1788-H1796 ◽  
Author(s):  
Scott S. Billecke ◽  
Laura A. Kitzmiller ◽  
Joseph J. Northrup ◽  
Steven E. Whitesall ◽  
Masumi Kimoto ◽  
...  
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Dominant Role ◽  
Peptide Bond ◽  
Sprague Dawley ◽  
Asymmetrical Dimethylarginine ◽  
Sprague Dawley Rats ◽  
Endogenous Nitric Oxide ◽  
Nos Inhibitor

The endogenous nitric oxide (NO) synthase (NOS) inhibitor asymmetrical dimethylarginine (ADMA) is elevated in many patients and may contribute to the initiation and progression of their disease. While some mechanistic pathways have been identified, tissue-specific contributions to ADMA control remain unclear. We sought to determine if whole blood (WB) could participate in ADMA control ex vivo. Anesthetized male Sprague-Dawley rats underwent exsanguinations, and WB preparations were incubated at 37°C for 5 h. ADMA and symmetrical dimethylarginine were analyzed by high-pressure liquid chromatography. Incubation of lysed red blood cell (RBC) supernatant yielded a significant decrease in ADMA that was blocked by 4124W, a synthetic inhibitor of dimethylarginine dimethylaminohydrolase, the only reported enzyme to hydrolyze ADMA. Hydrolysis of ADMA was diminished by addition of physiologically relevant concentrations of zinc (i.e., 20 μM). Conversely, when rat WB or WB supernatant was incubated at 37°C, it liberated quantities of free ADMA (1–2 μM) that in vivo would likely have pathological consequences. Addition of arginine methyltransferase inhibitors to these incubations did not reduce ADMA release, indicating no dominant role for active protein methylation during these incubations. This ADMA liberation was significantly reduced by addition of protease inhibitors, indicating a dependence on peptide bond hydrolysis. Total ADMA (protein incorporated plus free) was determined by acid hydrolysis and found to be 43.18 ± 4.79 μM in WB with ∼95% of this in RBCs. These ex vivo data demonstrate the potential of blood to control the NO-NOS system by modulating free ADMA.

scholarly journals Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries

2015 ◽  
Vol 309 (9) ◽  
pp. H1490-H1500 ◽  
Author(s):  
Ibolya Rutkai ◽  
Somhrita Dutta ◽  
Prasad V. Katakam ◽  
David W. Busija
Keyword(s):  
Mitochondrial Respiration ◽  
Ex Vivo ◽  
Cerebral Arteries ◽  
Anion Channel ◽  
Basal Respiration ◽  
Male Rat ◽  
Sprague Dawley ◽  
Voltage Dependent Anion Channel ◽  
Male And Female ◽  
Atp Production

Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using Nω-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I–V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury.

scholarly journals Early Effects of Tetraethylammonium Chloride on the Contractile Properties of Isolated Rabbit Basilar Arteries

1987 ◽  
Vol 7 (2) ◽  
pp. 237-247 ◽  
Author(s):  
A. R. Young ◽  
H. Säveland ◽  
J. D. Pickard ◽  
S. Perry ◽  
L. Brandt ◽  
...  
Keyword(s):  
Potassium Conductance ◽  
Cerebrovascular Reactivity ◽  
Maximal Response ◽  
Induced Response ◽  
Response Curves ◽  
Vascular Effects ◽  
Extracellular Medium ◽  
Tetraethylammonium Chloride ◽  
Basilar Arteries ◽  
The Right

The acute vascular effects of tetraethylammonium chloride (TEA) were examined on annular segments of rabbit basilar arteries, Contractions induced by the potassium channel blocker were compared with those obtained for potassium chloride, 5-hydroxytryptamine (5-HT) and norepinephrine (NE), The greater magnitude of the contractions was of the following order: [K+] > 5-HT> TEA> NK High concentrations of TEA alone (10−2 M) generated spontaneous oscillatory contractions in cerebral vessels that were normally quiescent, Low concentrations of TEA (10−8-10−6 M), which had no vasomotor properties per se, enhanced the contractile response of submaximal concentrations of 5-HT (10−7 M) and NE (3 × 10−6 M) and attenuated the contraction produced by 60 m M [K+], An increased vascular response to the amines was still evident up to 3 h after the addition of TEA despite frequent rinsing with fresh buffer solutions. On arteries precontracted with TEA (10−2 M), but not high [K +], the subsequent addition of 5-HT (10−7 M) still induced a powerful constriction. Repeated concentration-response curves for [K+] were reproducible and, in the presence of TEA (10−8 or 10−6 M), the curve was displaced to the right in a competitive manner. A higher concentration of TEA (10−4 M) was devoid of any blocking properties on the [K+]-induced response whereas, at 10−3 M TEA, the response was potentiated, as evidenced by a shift of the curve to the left. Interactions between TEA and the cumulative response to 5-HT were difficult to interpret. Repeated exposures of the artery to 5-HT resulted in an increased maximal response with each determination (EAm = 127 ± 9% and 149 ±: 14% of control values following the second and third applications, respectively). With TEA (10−6 M), the increase in the maximal contractile effect noted previously was not observed. Contractions induced by single concentrations of TEA (10−2 M) or [K+] (60 m M) were calcium dependent, were abolished completely in a calcium-free medium, and were depressed by the calcium antagonist nimodipine. 5-Hydroxytryptamine-induced contractions (10−5 M) were less sensitive to withdrawal of calcium from the extracellular medium (31 ± 6% relative to the maximal response at 4 m M calcium). Hence, an acute reduction in potassium conductance in cerebrovascular smooth muscle produced by TEA has complex, concentration-dependent effects and reproduces only part of the spectrum of effects of cisternal injection of blood on cerebrovascular reactivity.

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