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S164 Abstracts Heart, Lung and Circulation2007;16:S1–S201

a toxic gas. Interestingly, H2S is reported to be pro-duced in mammalian vascular smooth muscle cells by theenzyme cystathionine-�-lyase (CSE) and to have vasore-laxant effects. This study investigates the vasorelaxationresponse to exogenous H2S generated from NaHS. Inaddition, the vasorelaxation elicited from endogenouslyproduced H2S was examined by driving CSE with theaddition of its substrate L-cysteine. Mesenteric arteriesfrom male C57 mice were mounted in myographs, precon-tracted (∼50%) with U46619 and cumulative concentrationresponse curves to NaHS (1 �M–3 mM) or L-cysteine(10 nM–3 mM) were constructed. NaHS caused a bipha-sic vasorelaxation responses with pEC50(1) of 5.22 ± 0.29and pEC50(2) of 3.11 ± 0.21, n = 7. L-Cysteine also pro-duced a biphasic vasorelaxation response with pEC50(1)of 7.42 ± 0.38 and pEC50(2) of 3.01 ± 0.15, n = 6. Theresponse to L-cysteine was significantly inhibited by DL-propargylglycine (PPG, 20 mM, P < 0.05, 2-way ANOVA),an irreversible inhibitor of CSE. PPG (1 �M–20 mM)alone caused contraction when vessels were at rest-ing tone (25.4 ± 14.4% of maximum contraction inducedwith 120 mM K+ (KPSSmax), or in the presence of sub-maximal contraction with U46619 (1–10 nM; 17.9 ± 4.5%of KPSSmax), suggesting that the CSE enzyme has abasal activity in this preparation. These data indicate thatendogenous production of H2S is occurring in mousemesenteric arteries and contributes to vascular relaxation.

plaque (1.3–2.2-fold, P < 0.05), increased AR (2.2-fold,P < 0.05), decreased aromatase (2.3-fold, P < 0.005), andincreased 5AR expression (1.6-fold, P < 0.05). ER expres-sion remained high across all treatment groups.Conclusions: T has gender-specific effects on the devel-opment of atheroma. T is atheroprotective in males viaaromatisation to estradiol, which acts via the ER. By con-trast, T is proatherogenic in females mediated via theAR, due to decreased aromatase and increased 5AR. Thegender-specific effects of T has potential implicationsfor both men and women with this study highlightingthat hormonal regulation of aromatase, 5AR and AR areimportant considerations in our understanding of the safetherapeutic use of androgens.

doi:10.1016/j.hlc.2007.06.409

405Pulse Wave Analysis is a Reproducible Technique forNon-invasive Measurement of Central Blood Pressure andWave Reflection During Exercise

D.J. Holland 1,2,∗, J.W. Sacre 2, S.J. McFarlane 1, J.S.Coombes 2, T.H. Marwick 1, J.E. Sharman 1,2

1 University of Queensland, Department of Medicine, Brisbane4102, Australia; 2 School of Human Movement Studies, PrincessAlexandra Hospital, Brisbane 4102, Australia

doi:10.1016/j.hlc.2007.06.408

404Testosterone has Gender-specific Effects on Atherogenesis

M.D. Hill, K.C.Y. McGrath, D.S. Celermajer, D.J.Handelsman, A.K. Heather ∗

Heart Research Institute, Camperdown, New South Wales, Aus-tralia

Background: The major male hormone, testosterone (T),can be converted to estradiol (E) by aromatase or to dihy-drotestosterone (DHT) by 5alpha-reductase (5AR). E actsvia the estrogen receptor (ER) and DHT and T acts via theandrogen receptor (AR). We assessed the hypothesis thatT has gender-specific effects on atheroma formation viagender-specific conversion of T to its metabolites, E andDHT.Methods: Male and female ApoE−/− mice were assignedto control, castrate, and castrate + T treatment groups. Cas-tration was performed at 3–4 weeks of age, with micereceiving T replacement for 8–9 weeks. Lesion area wasthen measured by H&E staining. AR, ER, aromatase and5AR protein levels were measured by immunohistochem-istry.Results: Castration increased plaque in male and femalemice (1.8–2.9 and 1.3–1.9-fold, respectively, P < 0.05).In males, T decreased plaque (1.5–2.0-fold, P < 0.05),decreased AR (2.6-fold, P < 0.005), increased aromatase(1.3-fold, P < 0.05), and decreased 5AR expression (1.4-fold,P < 0.05). DHT (nonaromatisable) treatment did not pro-tect against plaque formation. In females, T increased

Background: There is emerging evidence that the cen-tral blood pressure (BP) response to exercise may havestronger prognostic value than resting BP measures alone.Pulse wave analysis (PWA) to measure central BP fromradial waveforms has been validated during exercise.However, the reproducibility of this technique has neverbeen reported, which was the aim of this study.Methods: Radial tonometry and PWA was used to derivecentral BP and augmentation index (AIx; a marker of wavereflection) during submaximal exercise (cycling at 50–60%of maximal predicted heart rate) and immediately aftermaximal treadmill exercise on two separate occasions.Submaximal waveforms were recorded by servocontrolledtonometry in 30 healthy subjects (aged 39 ± 13 years; 4with hypertension), and hand-held tonometry was usedto record post maximal waveforms in a separate group of20 healthy patients (aged 54 ± 10 years; 10 with type 2 dia-betes). Radial pressure waveforms were calibrated withbrachial BP measured by sphygmomanometry.Results: There was very good reproducibility betweentests for brachial and central systolic BP (SBP), pulsepressure (PP) and AIx (table). For both submaximaland maximal tests, there were no significant differencesbetween visits for exercise heart rate or mean arterial pres-sure (p > 0.05).Conclusion: Pulse wave analysis is a reproducible tech-nique for measurement of AIx and central BP duringexercise. The technique is, therefore, suitable for use inlarger intervention studies examining the clinical rele-vance of exercise central haemodynamics.