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Biomedical subjects

Bent Ottesen

Publications and source records attributed to Bent Ottesen.

At least 19 recordsLinked to original sources

Medroxyprogesterone acetate attenuates long-term effects of 17beta-estradiol in coronary arteries from hyperlipidemic rabbits.

OBJECTIVE: The progestin component in hormone replacement treatment may oppose the effects of estrogen on vascular function. This study examined the effect of long-term treatment with 17beta-estradiol (E(2)) alone and in combination with two progestins on K(+) and Ca(2+)-mediated mechanisms in coronary arteries. METHODS: Watanabe heritable hyperlipidemic rabbits were treated orally with either E(2) (4 mg/day), medroxyprogesterone acetate (MPA) (10 mg/day), norethindrone acetate (NETA) (2 mg/day), E(2)+MPA, E(2)+NETA, or placebo for 16 weeks (n=10 in each group). Coronary arteries were used for mRNA and myograph studies. RESULTS: E(2) increased vasodilatation induced by sodium nitroprusside and decreased vasocontraction induced by potassium. The first but not the latter response was opposed by MPA. The combination of MPA and E(2), but neither compound alone enhanced nimodipine-induced vasodilatation and increased the expression of L-type voltage-gated Ca(2+) channel mRNA. NETA had no opposing effects. Hormone treatment did not affect large-conductance Ca(2+) activated or ATP-sensitive K(+) channels or cGMP-dependent protein kinase mRNA expression. Hyperlipidemia had no effect on vascular reactivity. CONCLUSION: When E(2) is administered with MPA, effects of E(2) on nitric oxide and Ca(2+)-mediated vascular reactivity in rabbit coronary arteries are modulated. The results suggest that the progestin component in hormone replacement treatment may interfere with the supposed beneficial vascular effects of estrogen.

Animals↗

Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits.

OBJECTIVES: To evaluate the effect of estrogen replacement therapy or soy isoflavones supplement on endothelium-dependent relaxation in vitro and gene expression of endothelial nitric oxide synthase (eNOS) in cerebral arteries in a rabbit model of human hypercholesterolemia. STUDY DESIGN: Thirty-six female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomised to treatment with 17beta-estradiol (17beta-E(2)), SoyLife 150 or control for 16 weeks. Ring segments of basilar artery (BA) and posterior cerebral artery (PCA) were mounted in myographs for isometric tension recordings. Concentration response curves to carbamylcholine chloride, sodium nitroprusside (SNP) and l-NAME were evaluated after precontraction with potassium. Total RNA was extracted, reverse transcribed and eNOS quantitated by real-time polymerase chain reaction (real-time PCR). RESULTS: Plasma cholesterol was significantly higher at termination in the SoyLife group (P<0.0001), whereas low-density lipoprotein (LDL) cholesterol was comparable in all treatment groups. Neither treatment influenced the endothelium-dependent responses to carbamylcholine chloride or l-NAME or the endothelium-independent response to SNP in any of the arteries. Correspondingly, eNOS mRNA was similarly expressed in all treatment groups in both arteries. CONCLUSIONS: Improvement of cerebral endothelial function by estrogen or soy isoflavones in ovariectomized WHHL rabbits is not supported by the present data. The findings may be unique to the WHHL rabbit in which the hypocholesterolemic effect of estrogens mediated by upregulation of liver LDL receptors is excluded.

Animals↗

The effect of accelerated rehabilitation on recovery after surgery for ovarian malignancy.

BACKGROUND: In patients undergoing colonic surgery the postoperative hospital stay has been reduced from 8-12 days to 2-4 days with multimodal rehabilitation programs. The aim of this study was to evaluate the postoperative outcome after surgery for ovarian malignancy with conventional care compared to fast-track multimodal rehabilitation. METHODS: Seventy-two consecutive patients receiving conventional care (group 1) were compared with 69 consecutive patients receiving multimodal, fast-track rehabilitation with a planned care program including continuous epidural analgesia, early oral feeding and mobilization (group 2) in the same department. Outcome was postoperative hospital stay and morbidity during the first postoperative month. RESULTS: Median age was 63 years (group 1) and 62 years (group 2). Median postoperative hospital stay was reduced from 6 days in group 1 (mean 7.3) to 5 days in group 2 (mean 5.4) (p < 0.05). There was no difference in the overall complication rate, although severe medical complications were reduced in group 2 (14% versus 2%; p < 0.01). Readmission rate was 10% in group 1 and 3% in group 2 (p > 0.05). CONCLUSIONS: The concept of fast-track multimodal rehabilitation appears to be beneficial in patients operated for ovarian malignancy, as hospital stay and medical morbidity are reduced.

Adult↗

Maternal smoking predicts the risk of spontaneous abortion.

BACKGROUND: Few studies have examined smoking prior to pregnancy and the occurrence of spontaneous abortion, as most studies have addressed the risk of spontaneous abortion in relation to smoking during pregnancy. However, results are not entirely consistent. The aim of the present study was to assess the risk of spontaneous abortion considering smoking prior to pregnancy. METHODS: We performed a nested case-control study using prospective data from a population-based cohort comprising 11,088 women aged 20-29 years. From this cohort, women who experienced either a spontaneous abortion (n=343) or who gave birth (n=1,578) during follow-up were selected. Associations between self-reported smoking at enrollment and subsequent spontaneous abortion were analyzed by means of multiple logistic regression. RESULTS: The risk of spontaneous abortion in relation to pre-pregnancy smoking showed a clear dose-response effect. The adjusted odds ratio (95% confidence interval) for spontaneous abortion among current smokers prior to conception was 1.20 (1.04-1.39) per every extra five cigarettes smoked per day. The increased risk was only present for current smokers. The duration of smoking prior to pregnancy was not a significant predictor for subsequent spontaneous abortion. CONCLUSIONS: The amount of daily smoking prior to pregnancy seems to be associated with an increased risk of spontaneous abortion, whereas the duration of smoking does not seem to be related to an increased risk of spontaneous abortion.

Abortion, Spontaneous↗

The effect of environmental tobacco smoke during pregnancy on birth weight.

BACKGROUND: This study explores whether pregnant nonsmokers' exposure to environmental tobacco smoke (ETS) affects the average birth weight at term. METHODS: The population studied consists of pregnant nonsmokers participating in a study called Smoke-free Newborn Study. The participants (n = 1612) answered a questionnaire during 12th to 16th gestational week about their exposure to ETS at home and outside the home. RESULTS: Pregnant nonsmokers exposed to ETS both at home and outside the home gave birth to children with a birth weight of 78.9 g (95% CI -143.7 to -14.1) (P=0.02) lower than the weight of children born to women unexposed to ETS. There was no significant reduction in birth weight among women exposed to ETS at home only or outside the home only. A nonsignificant dose-response association was seen between increasing daily exposure to ETS and reduction in birth weight. CONCLUSION: Nonsmoking pregnant women who were exposed to ETS at home as well as outside the home gave birth to children with a 79 g reduction in birth weight compared to children of unexposed women. The fact that exposure to ETS has an effect on the birth weight is regarded as essential. The authors recommend that pregnant women should not be exposed to passive smoking, and that it should be considered whether workplace legislation should be instituted in order to protect pregnant women against the adverse effects of passive smoking.

Adult↗

The level of ADAM12-S in maternal serum is an early first-trimester marker of fetal trisomy 18.

BACKGROUND: ADAM12-S is a pregnancy-associated insulin-like growth factor binding protein-3 (IGFBP-3) and IGFBP-5 protease present in human gestational serum. Recently, maternal serum levels of ADAM12-S were found to be markedly reduced during the first trimester of pregnancies with a Down syndrome (DS) fetus. On the basis of this finding, it was suggested that ADAM12-S might be a useful maternal serum marker of fetal chromosomal disease. OBJECTIVE: Retrospective examination of the use of ADAM12-S as a marker for fetal trisomy 18. METHOD: Serum samples were obtained from ten women during the first semester of their pregnancies with fetuses that had trisomy 18. An ELISA was used to determine the levels of ADAM12 in maternal serum. Results were compared to ADAM12-S levels, previously measured in the serum of 170 women carrying normal pregnancies during the first trimester. RESULTS: In all cases, the ADAM12-S concentration in maternal serum samples was lower in trisomy 18 pregnancies than in normal pregnancies, with a median multiple of the median (MoM) of 0.28 (p < 0.001) CONCLUSION: A reduced concentration of ADAM12-S in maternal serum is a promising marker for foetal trisomy 18, as well as for DS.

ADAM Proteins↗

Reduction of the disintegrin and metalloprotease ADAM12 in preeclampsia.

OBJECTIVES: The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal growth. We examined whether the concentration of ADAM12 in first-trimester maternal serum could be used as a marker for preeclampsia. METHODS: We developed a semiautomated, time-resolved, immunofluorometric assay for the quantification of ADAM12 in serum. The assay detected ADAM12 in a range of 78-1248 microg/L. Serum samples derived from women in the first trimester of a normal pregnancy (n = 324) and from women who later developed preeclampsia during pregnancy (n = 160) were obtained from the First Trimester Copenhagen Study. ADAM12 levels were assayed in these serum samples. Serum levels of ADAM12 were converted to multiples of the median (MoM) after log-linear regression of concentration versus gestational age. RESULTS: Serum ADAM12 levels in women who developed preeclampsia during pregnancy had a mean log MoM of -0.066, which was significantly lower than the mean log MoM of -0.001 for ADAM12 levels observed in serum samples from women with normal pregnancy (P = .008). The mean log MoM was even lower in serum derived from preeclamptic women whose infant's weight at birth was less than 2,500 g (n = 27, mean log MoM of -0.120, P = .053). CONCLUSION: The maternal serum levels of ADAM12 are significantly lower during the first trimester in women who later develop preeclampsia during pregnancy when compared with levels in women with normal pregnancies. Because the secreted form of ADAM12 cleaves insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5, the IGF axis may play a role in preeclampsia. ADAM12 may be a useful early marker for preeclampsia. LEVEL OF EVIDENCE: II-2.

Adult↗

Women's experiences with short admission in abdominal hysterectomy and their patterns of behaviour.

The aim of this study was to describe how women experienced short admission in abdominal hysterectomy and to describe patterns of behaviours in short admission. A Short admission is now widely used in Denmark in relation to hysterectomy and involves one to two postoperative days. The diagnostic, prognostic and clinical indicators are well described in the literature. Documentation however, is sparse regarding the experiences of the women involved. This article presents and discusses the women's own experiences and the impact of the short admission. The results are part of a lager evaluation of women and staff experiences overall. The design is exploratory and descriptive. Ten women who underwent a hysterectomy were selected consecutively from August 2001 and were followed from their initial examination to 1 month following hospital discharge. Data were collected by individual interviews. To grasp a complex reality and patterns of behaviour a typical-type methodology were used. As a result three types of women were identified: (i) The intervening type, (ii) the cooperative type and (iii) the unsure type. The women considered dialogue with the staff to be essential in short admissions. Women in this study who described emotional reactions considered it important that staff do not refrain from speaking about sensitive subjects. In conclusion the importance of dialogue creates new demands for the staff, as somatic care in this context has changed to be more oriented towards information and follow-up. The women in this study did not have any physical side effects but reported some psychological areas of importance. An outpatient clinic staffed by nurses could cover the needs of the woman.

Adult↗

Progestins used in hormonal replacement therapy display different effects in coronary arteries from New Zealand white rabbits.

OBJECTIVES: The aim of this study was in an animal model to assess the vascular effects of different progestins commonly used in hormonal replacement treatment. METHODS: Fifty-six non-atherosclerotic, ovariectomized New Zealand white rabbits were randomized into seven groups: (1) medroxyprogesterone acetate (MPA), (2) norethisterone acetate (NETA), (3) conjugated equine estrogens (CEE), (4) 17-beta-estradiol (E2), (5) MPA+CEE , (6) NETA+E2 , (7) or placebo (n=8) and given hormonal treatment through the diet for 4 weeks. Ring segments from the left proximal coronary artery and from the distal part of the left anterior descending coronary artery were microdissected and mounted for isometric tension recordings in a myograph. The vasoconstrictory responses induced by potassium, endothelin-1, calcium and Nw-nitro-L-arginine methyl ester, and the vasodilatory response induced by acetylcholine and sodiumnitroprusside were investigated. The maximum contraction/relaxation (Emax) and the concentration required to induce half the maximum response (EC50) were determined. EC50 values were expressed as the negative logarithm to the molar concentration, pD2=-log EC50. RESULTS: Treatment with MPA alone caused when compared to treatment with NETA an increase in tension development in the distal coronary artery after the addition of potassium ( 6.36+/-0.36 versus 4.31+/-0.42 P<0.005) (single dose response, mN/mm, mean+/-S.E.M.) and endothelin-1 (9.41+/-0.82 versus 6.43+/-0.73 P<0.05) (Emax, mN/mm, mean+/-S.E.M.). Treatment with MPA compared to placebo caused an endothelin-1 induced increase of Emax in the distal coronary artery (9.21+/-0.87 versus 6.51+/-0.65 P<0.05) and a calcium induced increase of pD2 in both coronary arteries (2.98+/-0.19 versus 2.42+/-0.12 P<0.05, proximal coronary artery) (3.26+/-0.09 versus 2.9+/-0.1 P<0.05, distal coronary artery) (pD2, mean+/-S.E.M.). Treatment with NETA compared to placebo in the proximal coronary artery, after the addition of sodiumnitroprusside caused a decrease of pD2 (5.33+/-0.19 versus 5.94+/-0.13 P<0.05). Treatment with E2 compared to treatment with CEE in the proximal coronary artery caused a decrease of pD2 after the addition of sodiumnitroprusside (5.00+/-0.16 versus 5.77+/-0.28 P<0.05). No significant differences were found between MPA+CEE and NETA+E2. CONCLUSION: Treatment with MPA alone seems to enhance the contractile response to potassium and endothelin-1 in the distal coronary artery compared to NETA, indicating that different progestins used in hormonal replacement treatment may display different effects on contractile functions of coronary arteries.

Acetylcholine↗

Tibolone and its metabolites acutely relax rabbit coronary arteries in vitro.

OBJECTIVES: To compare the acute effects of estradiol, tibolone and its metabolites on coronary arteries in vitro and to investigate possible vascular mechanisms. METHODS: Coronary artery ring segments from female rabbits were mounted in myographs for isometric tension recordings. Concentration-response curves to tibolone, 3 alpha-OH-tibolone, 3 beta-OH-tibolone, Delta 4-isomer and 17 beta-estradiol were obtained after precontraction with potassium 30 mmol/l and after addition of N omega-nitro-l-arginine methyl ester 10(-4) mol/l (l-NAME, an inhibitor of endothelial nitric oxide (NO) synthase) or tetraethylammonium chloride 10(-2) mol/l (TEA, an unspecific inhibitor of potassium channels). The effects of the different substances to calcium concentration-response curves were evaluated. Responses are expressed as maximal contraction (E max), concentration giving half maximal contraction (log EC50) or area under curve (AUC). RESULTS: Tibolone and its metabolites induced a concentration-dependent vasodilatation comparable to that of 17 beta-estradiol with the rank of potency: 3 beta-OH-tibolone approximately = to tibolone>3 alpha-OH-tibolone>Delta 4-isomer (ANOVA). l-NAME partly inhibited the relaxation to all substances. TEA induced a slight rightward shift of the relaxation to 3 alpha-OH-tibolone (log EC50: -5.05 versus -5.20; P<0.05; Student's t-test), but not to the other substances. Calcium concentration-dependent contraction curves were inhibited by all substances compared to controls (AUC, P<0.05, ANOVA). CONCLUSIONS: Our data indicate that the acute relaxation induced by tibolone and its metabolites in coronary arteries in vitro are probably mediated by endothelium independent inhibition of calcium channels but may also involve an endothelium-dependent mechanism via nitric oxide. The effect of tibolone is comparable to that of 17 beta-estradiol in this set-up.

Animals↗

Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe.

Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases were ascertained using nationwide registries. The follow-up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were performed using Cox proportional hazards model. A total of 244 women developed breast cancer during follow-up. After adjustment for confounding factors, an increased risk of breast cancer was found for the current use of estrogen only (RR = 1.96; 95% CI = 1.16-3.35), for the combined use of estrogen and progestin (RR = 2.70; 95% CI = 1.96-3.73) and for current users of tibolone (RR = 4.27; 95% CI = 1.74-10.51) compared to the never use of HRT. In current users of combined HRT with testosterone-like progestins, the continuous combined regimens were associated with a statistically significant higher risk of breast cancer than the cyclical combined regimens (RR = 4.16, 95% CI = 2.56-6.75, and RR = 1.94, 95% CI = 1.26-3.00, respectively). An increased risk of breast cancer was noted with longer durations of use for the continuous combined regimens (p for trend = 0.048). The European traditional HRT regimens were associated with an increased risk of breast cancer. The highest risk was found for the use of continuous combined estrogen and progestin.

Aged↗

Why do slim women consider themselves too heavy? A characterization of adult women considering their body weight as too heavy.

OBJECTIVE: The purpose of this study was to characterize women who, in spite of a low body mass index (BMI), considered themselves too heavy. METHOD: Of 11,905 women (27-38 years of age), we focused on 2,443 nonpregnant women with a low BMI (18.5-21.0 kg/m(2)), who considered their weight acceptable or too heavy. Participants completed a comprehensive questionnaire. By multiple logistic regression we examined associations between lifestyle and health variables and the risk of considering own body weight too heavy. RESULTS: Approximately 10 % considered their body weight too heavy. Risk factors included early severe life events, young age at start of risky lifestyle behaviors, weight fluctuation, self-reported lifetime history of eating disorders, perception of too heavy workload, and poor physical form and self-rated health. Body dissatisfaction decreased with increasing age. DISCUSSION: Our results indicate that body dissatisfaction is established in childhood and adolescence. It is unknown if this body dissatisfaction influences the life of the women, but it might influence the values they pass on to their children.

Adolescent↗

Measurement of aortic blood flow by magnetic resonance below and above the origin of the coronary arteries in postmenopausal hormone replacement therapy.

PURPOSE: Principal blood flow measures might be assessable by velocity-encoded cine magnetic resonance (VENC MR) of aortic blood flow. The feasibility of using VENC MR for clinical research was tested in a contemporary and controversial human model: the effects of 17beta-estradiol (E) and cyclic norethisterone acetate (NETA) in postmenopausal women. METHODS: Sixteen postmenopausal women were included in a crossover study (two 12-week periods, 3-month washout) and randomized to E and NETA or placebo. Aortic blood flow (ABF) was measured eight times by VENC MR below and above the coronary arteries (CA) and was used for estimation of coronary artery blood flow (CABF) and peak flow velocity (Vmax). The calculated value of CABF was negative and was corrected by averaging systolic flow. Data were analyzed in a repeated measurement model including analysis of repeatability (CR) and group variability (CV). RESULTS: The CR and CV of ABF were low (11% and 7%) and corresponded at the two levels. Vmax showed similar levels of reproducibility at the two levels. The coronary artery blood flow was less reproducible (39% and 31%). During treatment, ABF above CA was reduced after 12 weeks (p=0.03), ABF below CA was unchanged, and CABF was significantly increased without detrimental effects of NETA. Vmax was increased at NETA addition (p<0.01). CONCLUSIONS: Aortic flow quantification by VENC MR is reproducible and useful for assessment of principal haemodynamic changes in smaller studies. Derived measurement of CABF lacks precision. Differences in change below and above CA indicate that oral high-dose E and NETA may induce coronary artery dilatation.

Aorta↗

Patient and staff (doctors and nurses) experiences of abdominal hysterectomy in accelerated recovery programme. A qualitative study.

INTRODUCTION: The accelerated recovery programme (ARP) is becoming commonplace in surgical specialties and has also been introduced to hysterectomy patients. Diagnostic, prognostic and other clinical indicators are well described. The aim of this article is to relay knowledge about the ARP, through the experiences of the women operated and the staff involved. MATERIAL AND METHODS: The study is exploratory and descriptive, using qualitative methods. Seventeen women, with good health status, were consecutively selected from August to September 2001. The women were observed and ten were interviewed twice, at discharge and one month following their return home. The staff (n = 15) were interviewed individually and/or participated in focus group interviews before (February 2001) and following (November 2001) the introduction of the ARP. RESULTS: The women experienced little difficulty with the ARP. They defined themselves as being good girls but expressed that when the hospital's ARP had expired the attention from the staff declined. The staff continued to be concerned about whether the women received the information and psychological care they needed but claimed that the ARP proved better for the women than they had expected. CONCLUSION: The ARP did not appear to be a burden for the women involved in the study; however, it did not consider individual needs for psychological care. Future efforts should ensure a thorough introduction of the ARP to new staff as well as illustrative material for purposes of information relay and dialogue between staff and patients/family members. A nursing care ambulatory unit is recommended to support with information for women prior to and following hysterectomy in the ARP.

Adult↗

ADAM12: a novel first-trimester maternal serum marker for Down syndrome.

OBJECTIVES: The concentration of bioavailable insulin-like growth factor (IGF) I and II is important to foetal growth. It is regulated by insulin-like growth factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP-3 takes place in human pregnancy serum; accordingly, IGFBP-3 serum levels decrease markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP-3 and IGFBP-5 protease and is present in human pregnancy serum. The goal of this study was to determine whether ADAM12 concentration in maternal serum is a useful indicator of foetal health. METHODS: We developed an enzyme-linked immunosorbent assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42 to 667 micro g/L. Recombinant ADAM12 was used as the standard for calibration. RESULTS: We found that ADAM12 was highly stable in serum. Serum concentration increased from 180 micro g/L at week 8 of pregnancy to 670 micro g/L at 16 weeks, and reached 12 000 micro g/L at term. In 18 first-trimester Down syndrome pregnancies, the concentration of ADAM12 was decreased, thus the median multiple of mean (MoM) value was 0.14 (0.01-0.76). A detection rate for foetal Down syndrome of 82% for a screen-positive rate of 3.2% and a 1:400 risk cut-off was found by Monte Carlo estimation using ADAM12 and maternal age as screening markers. CONCLUSION: ADAM12 is a promising marker for Down syndrome.

ADAM Proteins↗

Long-term estradiol treatment improves VIP-mediated vasodilation in atherosclerotic proximal coronary arteries.

The aim of the present study was to evaluate the impact of long-term estrogen replacement therapy (ERT) on the vasodilatory effect of the two peptides vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) in atherosclerotic coronary and cerebral arteries. Female ovariectomized homozygous Watanabe heritable hyperlipidemic rabbits were randomized to 16 weeks treatment with 17beta-estradiol or placebo. The diet was semisynthetic, thereby avoiding the influence of phytoestrogens. Artery ring segments were mounted for isometric tension recordings in myographs. Following precontraction, the dose-response relationships for VIP and PACAP were evaluated.Treatment with 17beta-estradiol significantly improved the maximum VIP-mediated vasodilation (E(max), percentage of precontraction) in proximal coronary arteries (45.8+/-9.6% vs. 24.1+/-3.7%, p<0.05). In the same artery segment, 17beta-estradiol induced a significant decrease in the relative ratio between the repeated contractile response to potassium 30 and 120 mM (100+/-7% vs. 132+/-11%, p<0.05). For distal coronary arteries, there was a tendency to similar changes, but no statistical differences for the potassium or VIP responses in cerebral or distal coronary arteries were found between the two groups. 17beta-estradiol induced no changes in the PACAP-mediated vasodilation. These results suggest that long-term treatment with 17beta-estradiol improves the VIP-mediated but not the PACAP-mediated vasodilation in atherosclerotic proximal coronary arteries.

Animals↗

VIP and PACAP display different vasodilatory effects in rabbit coronary and cerebral arteries.

Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are closely related peptides with wide distribution in the nervous system. The aim of the present study was to investigate functional characteristics and the influence of sex steroids on the vasodilatory effects of these two peptides in cerebral and coronary vessels from female New Zealand White (NZW) rabbits. The localization and concentration of VIP and PACAP in cardiovascular tissue was evaluated using immunohistochemistry and radioimmunoassays. The vasodilatory effects of VIP and PACAP were investigated using myographs, allowing isometric tension recordings. In order to evaluate the influence of steroid hormones, the rabbits were ovariectomized and randomized to treatment for 4 weeks with 17beta-estradiol (E(2)), Norethindrone Acetate (NETA), E(2)+NETA or placebo. Ring segments of the posterior cerebral artery, the right proximal coronary artery and the distal left coronary artery were examined. The highest concentrations of VIP/PACAP were observed in cerebral and coronary arteries: 5.0/5.7 and 2.8/3.5 pmol/g, respectively. The peptides were localized in nerve fibres innervating the arteries. Both peptides produced dose-dependent vasodilatory responses in all vessels investigated. While the effects of PACAP were identical in cerebral and coronary arterial segments, the effects of VIP displayed significant differences (E(max), pI(2), Hill-slope). Treatment with sex steroids induced no changes in the vascular effects of the two peptides. These results indicate different mechanisms of action for the vasodilating effects of the two closely related peptides VIP and PACAP in different areas of the coronary and cerebrovascular tree. Treatment with female sex steroids does not seem to change these mechanisms.

Animals↗