Role of endothelium in sexual dimorphism in vasopressin-induced contraction of rat aorta

1993 ◽  
Vol 265 (6) ◽  
pp. H2073-H2080 ◽  
Author(s):  
J. N. Stallone
Keyword(s):  
Contractile Response ◽  
Rat Aorta ◽  
Isometric Tension ◽  
No Synthase ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Phenylephrine Hydrochloride ◽  
Rat Thoracic Aorta ◽  
Increased Sensitivity

In rat thoracic aorta, contractile responses to arginine vasopressin (AVP) are twofold higher in females than in males. To determine the role of the endothelium in this phenomenon, the effects of endothelium removal and inhibition of nitric oxide (NO) synthase and cyclooxygenase were examined in thoracic aortas prepared from male and female Sprague-Dawley rats and mounted for isometric tension recording. Maximal contractile response to AVP was substantially higher in female (4,232 +/- 316 mg/mg ring dry wt) than in male aortas (1,365 +/- 239; P < 0.01). Removal of the endothelium markedly potentiated maximal response to AVP in male aortas (4,100 +/- 422 mg/mg ring wt; P < 0.01); endothelium removal increased sensitivity but not maximal response in female aortas. Inhibition of NO synthase with NG-monomethyl-L-arginine (L-NMMA, 250 microM) doubled maximal contraction to AVP in male aortas (3,175 +/- 193 mg/mg ring wt; P < 0.01); L-NMMA increased sensitivity but not maximal response in female aortas. Inhibition of cyclooxygenase with indomethacin (10 microM) did not alter maximal response to AVP in male aortas but significantly attenuated responses of female aortas (2,816 +/- 306 mg/mg ring wt; P < 0.01). In contrast, maximal contractile response to phenylephrine hydrochloride (PE) was 40% higher in males than in females (P < 0.01); L-NMMA increased both the sensitivity and maximal response to PE to a greater extent in female (3,061 +/- 121 vs. 4,971 +/- 135 mg/mg ring wt; P < 0.01) than in male aortas (4,317 +/- 227 vs. 4,899 +/- 104 mg/mg ring wt; P < 0.01). (ABSTRACT TRUNCATED AT 250 WORDS)

Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K+ channel activation

2001 ◽  
Vol 91 (6) ◽  
pp. 2742-2750 ◽  
Author(s):  
Andrew Q. Ding ◽  
John N. Stallone
Keyword(s):  
Rank Order ◽  
Specific Effect ◽  
Rat Aorta ◽  
Isometric Tension ◽  
K Channel ◽  
Delayed Rectifier ◽  
Sprague Dawley ◽  
Voltage Dependent ◽  
Rat Thoracic Aorta ◽  
Lower Permeability

Recent studies have established that testosterone (Tes) produces acute (nongenomic) vasorelaxation. This study examined the structural specificity of Tes-induced vasorelaxation and the role of vascular smooth muscle (VSM) K+ channels in rat thoracic aorta. Aortic rings from male Sprague-Dawley rats with (Endo+) and without endothelium (Endo−) were prepared for isometric tension recording. In Endo− aortas precontracted with phenylephrine, 5–300 μM Tes produced dose-dependent relaxation from 10 μM (4 ± 1%) to 300 μM (100 ± 1%). In paired Endo+ and Endo− aortas, Tes-induced vasorelaxation was slightly but significantly greater in Endo+ aortas (at 5–150 μM Tes); sensitivity (EC50) of the aorta to Tes was reduced by nearly one-half in Endo− vessels. Based on the sensitivity (EC50) of Endo− aortas, Tes, the active metabolite 5α-dihydrotestosterone, the major excretory metabolites androsterone and etiocholanolone, the nonpolar esters Tes-enanthate and Tes-hemisuccinate (THS), and THS conjugates to BSA (THS-BSA) exhibited relative potencies for vasorelaxation dramatically different from androgen receptor-mediated effects observed in reproductive tissues, with a rank order of THS-BSA > Tes > androsterone = THS = etiocholanolone > dihydrotestosterone ≫ Tes-enanthate. Pretreatment of aortas with 5 mM 4-aminopyridine attenuated Tes-induced vasorelaxation by an average of 44 ± 2% (25–300 μM Tes). In contrast, pretreatment of aortas with other K+ channel inhibitors had no effect. These data reveal that Tes-induced vasorelaxation is a structurally specific effect of the androgen molecule, which is enhanced in more polar analogs that have a lower permeability to the VSM cell membrane, and that the effect of Tes involves activation of K+ efflux through K+channels in VSM, perhaps via the voltage-dependent (delayed-rectifier) K+ channel.

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)

Endotoxin enhances hypoxic constriction of rat aorta and pulmonary artery through induction of EDRF/NO synthase

1993 ◽  
Vol 265 (4) ◽  
pp. L346-L354 ◽  
Author(s):  
P. Zelenkov ◽  
T. McLoughlin ◽  
R. A. Johns
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Pulmonary Artery ◽  
Contractile Response ◽  
Rat Aorta ◽  
Isometric Tension ◽  
No Synthase ◽  
Vascular Response ◽  
Hypoxic Vasoconstriction ◽  
The Right

The vascular response to hypoxia in endotoxin (lipopolysaccharide; LPS)-exposed rat pulmonary artery (PA) and thoracic aorta (AO) was investigated and the mechanism of the observed hypoxic responses defined. In isometric tension studies, LPS-treated AO and PA rings, with and without endothelium, demonstrated decreased (P < 0.05) contractile response to phenylephrine (PE EC50), and the dose response was shifted to the right (P < 0.01) compared with non-LPS treated rings. Both vessel types responded to hypoxia with a markedly increased (P < 0.01) and sustained (P < 0.01) constriction when preexposed to LPS. Control non-LPS rings with endothelium intact had a transient vasoconstriction in early hypoxia, which was abolished with removal of the endothelium. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, increased the PE EC50 tension in LPS-treated rings, markedly reduced the duration and magnitude of the hypoxic vasoconstriction in LPS-treated rings, and attenuated the transient vasoconstriction seen in endothelium-intact, non-LPS rings (all P < 0.05). L-Arginine reversed the L-NAME effects. Hypoxia decreased guanosine 3',5'-cyclic monophosphate (cGMP) content 54 +/- 4% in all LPS and 33 +/- 4% in the non-LPS intact rings (P < 0.05). L-NAME reduced cGMP content 90 +/- 5% in all LPS rings. Indomethacin inhibited formation of a constriction factor in aortic LPS-treated rings (P < 0.01) that was endothelium dependent and unaffected by the presence of L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Sexual dimorphism in prostanoid-potentiated vascular contraction: roles of endothelium and ovarian steroids

2002 ◽  
Vol 283 (5) ◽  
pp. H2062-H2073 ◽  
Author(s):  
Clifford T. Fulton ◽  
John N. Stallone
Keyword(s):  
Sexual Dimorphism ◽  
Vascular Reactivity ◽  
Contractile Response ◽  
Rat Aorta ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Similar Extent ◽  
Contractile Responses ◽  
Ovarian Steroids ◽  
Sprague Dawley Rats

The effects of constrictor prostanoid (CP) pathway inhibitors on vascular reactivity to vasopressin (VP) and phenylephrine (PE) were examined in thoracic aortas of male, female, and ovariectomized (OVX) female Sprague-Dawley rats. Maximal contractile response of control (Cont) aortas to VP was markedly higher in females (3,885 ± 332 mg/mg ring wt) than in males (810 ± 148 mg). Indomethacin (Indo; 10 μM) attenuated maximal response to VP in females (3,043 ± 277 mg) but not in males. SQ-29,548 (SQ; 1 μM) attenuated maximal response to VP in females (3,042 ± 290 mg) to a similar extent as Indo. Dazoxiben (Daz; 10 μM) alone had no effect, but Daz + SQ attenuated maximal contractile response to VP to a similar extent as SQ alone. Removal of the endothelium in female aortas attenuated contractile responses to VP in Cont aortas. OVX attenuated maximal contractile response to VP in Cont aortas (2,093 ± 329 mg) and abolished the attenuating effects of Indo. Indo, SQ, and Daz exerted identical effects on contractile responses of male, female, and OVX female aortas to PE. These findings establish the following in the rat aorta: 1) CP, probably thromboxane and/or endoperoxide, is responsible for ∼25–30% of contractile responses of females, but not males, to VP and PE; 2) CP production by the female aorta is primarily endothelial in origin; and 3) ovarian steroids modulate production and/or actions of CP in female aortas.

Inducible nitric oxide synthase and vascular reactivity in rat thoracic aorta: effect of aminoguanidine

1996 ◽  
Vol 80 (1) ◽  
pp. 271-277 ◽  
Author(s):  
J. A. Scott ◽  
M. Machoun ◽  
D. G. McCormack
Keyword(s):  
Nitric Oxide ◽  
Vascular Reactivity ◽  
Vascular Tissue ◽  
Contractile Response ◽  
Selective Inhibition ◽  
No Synthase ◽  
Sprague Dawley ◽  
Vascular Contractility ◽  
Inducible No Synthase ◽  
Rat Thoracic Aorta

We tested the hypothesis that selective inhibition of the inducible form of nitric oxide (NO) synthase with aminoguanidine would prevent the loss of vascular contractility after exposure to endotoxin [lipopolysaccharide (LPS)]. Aortic rings were dissected from Sprague-Dawley rats, suspended in organ baths containing Krebs solution, and tested for vascular reactivity. Vessels incubated with LPS (1 microgram/ml) for 5 h exhibited a significant decrease in the maximal contractile response to phenylephrine. Aminoguanidine (100 microM) restored the maximal contractile response of LPS-treated vessels to the level of the control vessels. Aminoguanidine was approximately 250-fold less potent than NG-nitro-L-arginine methyl ester in inhibiting the constitutive NO synthase in vascular tissue as determined by its ability to further increase tone of submaximally contracted aortic rings. NO synthase activity was determined in vascular tissue incubated with and without LPS. Vessels incubated with LPS exhibited a marked increase in the levels of inducible NO synthase activity compared with control vessels. This increase was restored to control levels when tissue homogenates were incubated with aminoguanidine. We conclude that aminoguanidine is a selective concentration-dependent inhibitor of the inducible form of NO synthase and may be a useful probe to evaluate the role of inducible NO synthase in the abnormal vascular contractility characteristic of endotoxemia and sepsis.

Abstract 579: Increased Role of COX-derived Prostanoids in Regulating Ang II Induced Uterine Artery Contraction at Early Pregnancy in a Transgenic Model of Preeclampsia

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Victor M Pulgar ◽  
Liliya M Yamaleyeva ◽  
Jasmina Varagic ◽  
Carolynne M McGee ◽  
Michael Bader ◽  
...  
Keyword(s):  
Uterine Artery ◽  
Inhibitory Effect ◽  
Isometric Tension ◽  
Late Gestation ◽  
Female Rat ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Vascular Control ◽  
Human Renin

The balance between vasodilatory and vasoconstrictor prostanoids contributes to vascular control during pregnancy. Alterations in this balance are involved in the development of hypertensive pregnancy. The transgenic female rat containing the human angiotensinogen (hAGN) gene mated with the male transgenic containing human renin (hREN) is a model of preeclampsia (TgA), and shows hypertension and proteinuria at late gestation. We investigated the role COX-derived mediators have on contractility of the uterine artery (UA) in TgA rats before the hypertensive phenotype develops. UA were isolated from transgenic TgA (n=9) and Sprague-Dawley (n=7) control rats at 7 days of gestation. UA were mounted in a wire myograph for determinations of isometric tension (DMT USA, 620M). Responses to acetylcholine (ACh), phenylephrine (Phe) and sodium nitroprusside (SNP) were measured in control conditions and after preincubation with indomethacin (Indo, 10-5M). Data were fitted to a dose response curve, vasodilatation was expressed as percent of pre-constriction and sensitivity as pD2 (pD2= -Log [EC50]). Responses to ACh reached similar maximal relaxations (64±8 vs 75±6%, p>0.05), and an increased contraction in TgA UA at ACh >10μM (p<0.05) was eliminated by Indo. Contraction to Phe was similar in both groups with an inhibitory effect of Indo on TgA UA (p<0.05). Relaxation to SNP was lower in TgA vs SD UA (92±2 vs 74±5%, p<0.05), this difference was abolished by Indo. Thus, inhibition of COX enzymes had a greater effect on TgA UA suggesting an imbalance towards an increased prostanoids-derived constrictor tone in TgA UA. This imbalance appears before the hypertensive phenotype is established.

Effects of forskolin and cyclic nucleotides on isometric force in rat aorta

1986 ◽  
Vol 250 (3) ◽  
pp. C468-C473 ◽  
Author(s):  
E. G. McMahon ◽  
R. J. Paul
Keyword(s):  
Cyclic Nucleotides ◽  
Cyclic Nucleotide ◽  
Isometric Force ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Tension Development ◽  
Nucleotide Analogues ◽  
Cyclic Monophosphate ◽  
Contractile System ◽  
Rat Thoracic Aorta

The present study was undertaken to determine the extent to which cyclic nucleotide-induced relaxation in the intact rat aorta is mediated at the level of the contractile system. The relaxant effects of the cyclic nucleotide analogues [8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) and dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP)] and forskolin were examined in both the intact vessel and a Triton X-100-skinned preparation of rat thoracic aorta. Relaxation of a norepinephrine-induced contraction was essentially complete 30 min after the addition of 50 microM 8-BrcGMP [% relaxation = 87.2 +/- 4.4% (n = 4)], 100 microM DBcAMP [98.2 +/- 1.2% (n = 4)], and 1 microM forskolin [107.0 +/- 3.3% (n = 5)]. These same doses were ineffective in relaxing precontracted skinned rat aortic rings compared with the relaxation achieved in the intact vessel. The largest relaxation in the skinned aortas was achieved with the addition of 1 microM forskolin [17.4 +/- 1.5% (n = 4)]. The addition of catalytic subunit of cAMP-dependent protein kinase had no effect on isometric tension in the precontracted skinned aorta. Preincubation with the cyclic nucleotide analogues or forskolin in a low-Ca2+ solution (pCa less than 8) was also ineffective in inhibiting subsequent isometric tension development. Our results suggest that only a very small fraction of the relaxation with cyclic nucleotides and forskolin in the intact rat aorta is due to the action of these agents at the level of the contractile system.

Androgen-receptor defect abolishes sex differences in nitric oxide and reactivity to vasopressin in rat aorta

2001 ◽  
Vol 91 (6) ◽  
pp. 2602-2610 ◽  
Author(s):  
John N. Stallone ◽  
Ronald L. Salisbury ◽  
Clifford T. Fulton
Keyword(s):  
Nitric Oxide ◽  
Androgen Receptor ◽  
Methyl Ester ◽  
Thoracic Aorta ◽  
Vascular Reactivity ◽  
Rat Aorta ◽  
Maximal Response ◽  
Maximal Contraction ◽  
Rat Thoracic Aorta ◽  
Recessive Defect

Contractions of rat thoracic aorta to vasopressin (VP) are threefold higher in females (F) than in males (M), primarily because nitric oxide (NO) attenuation of contraction is greater in M. To determine the role of the androgen receptor (AR) in this mechanism, vascular reactivity to VP was examined in thoracic aorta of the testicular-feminized male (Tfm) rat, which has an X-linked, recessive defect in AR function in affected M. Maximal contraction of normal aortas to VP was fourfold higher in F (4,128 ± 291 mg/mg ring wt) than in M (971 ± 133 mg); maximal response of Tfm (3,967 ± 253 mg) was similar to that of normal F. N G-nitro-l-arginine methyl ester increased maximal response to VP threefold in M but had no effect in F or Tfm. In contrast, maximal contraction of normal aortas to phenylephrine was 43% higher in M (4,011 ± 179 mg) than in F (2,809 ± 78 mg); maximal response of Tfm (2,716 ± 126 mg) was similar to that of normal F. N G-nitro-l-arginine methyl ester increased maximal response to phenylephrine by >50% in F and Tfm but had no effect in M. Maximal contractile response to 80 mM KCl did not differ among M, F, or Tfm. Thus androgens and normal vascular AR function are important in the greater NO-mediated attenuation of reactivity to VP in M than in F rat aorta, which may involve specific modulation of endothelial VP signal transduction pathways and NO release by androgens. These data also establish the importance of the Tfm rat as a model to study the effects of androgens on cardiovascular function.

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.

Endothelial and vascular smooth muscle responses are altered after left lung autotransplantation

1994 ◽  
Vol 266 (5) ◽  
pp. H2026-H2032 ◽  
Author(s):  
N. A. Flavahan ◽  
T. D. Aleskowitch ◽  
P. A. Murray
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Left Lung ◽  
Calcium Ionophore ◽  
Selective Reduction ◽  
Isometric Tension ◽  
Maximal Response ◽  
No Donor ◽  
Significant Difference ◽  
Increased Sensitivity

Left lung autotransplantation (LLA) increased the pulmonary vasoconstriction evoked by phenylephrine and attenuated the vasodilatation caused by acetylcholine or bradykinin in conscious dogs. To study the mechanisms responsible for these changes, pulmonary arterial rings were isolated from right (control) and left (LLA) lower lobes of dogs 1-26 mo after LLA and were suspended for isometric tension recording. Compared with control rings from the same anatomic location, contractions to phenylephrine were increased after LLA in rings with or without endothelium. In arterial rings contracted to 50% of their maximal response to phenylephrine, acetylcholine, bradykinin, and calcium ionophore caused endothelium-dependent relaxations that were reduced in LLA compared with control rings. In arterial rings from control and LLA lungs, relaxations to acetylcholine were not altered by inhibition of cyclooxygenase (indomethacin) but were reduced after inhibition of NO synthase [N omega-nitro-L-arginine methyl ester (L-NAME)]. After L-NAME, there was no longer any significant difference in acetylcholine-induced relaxation between arterial rings from control and LLA lungs. Relaxation to SIN-1, a NO donor, was similar in arterial rings (without endothelium) from control and LLA lungs. The results suggest that LLA causes an increased sensitivity of vascular smooth muscle to alpha 1-adrenergic activation and endothelial dysfunction that is mediated by a selective reduction in the activity of endothelium-derived relaxing factor/NO.

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