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Biomedical subjects

K E Clark

Publications and source records attributed to K E Clark.

At least 19 recordsLinked to original sources
PubMed2003

Uterine blood flow--a determinant of fetal growth.

An adequate increase of uterine blood flow throughout gestation is essential for uterine, placental and fetal growth. Maternal cardiovascular adaptation has to provide the uterine perfusion that is necessary to meet the requirements of the developing and growing fetus by providing transport of nutrients and oxygen to the placenta and the fetus. Thus, uterine blood flow is inextricably linked to fetal growth and survival. Reductions of uterine blood flow can occur under acute or chronic conditions or in a combination of both. Chronic reductions of uterine blood flow can be observed in pregnancy-induced hypertension (PIH), diabetes mellitus in pregnancy and intrauterine growth restriction (IUGR). Chronic restrictions in uterine blood flow will elicit a placental and fetal response in the form of growth adaptation to the reduced supply of oxygen and nutrients to the conceptus. If compensatory growth restriction reaches its limits intrauterine fetal distress can ensue. Among the great number of experimental models of intrauterine growth restriction, those involving a generalized reduction in the uteroplacental blood supply are of significance to questions relating to human pregnancy. Despite physiological differences, particularly with regard to maternal metabolism and placentation, the occlusion model in the pregnant sheep is suitable for investigating questions about fetal and placental growth.

Animals↗
PubMed2002

Correcting for signal saturation errors in the analysis of microarray data.

A variety of technical errors have arisen in data analysis when using cDNA or oligonucleotide microarrays. One of the most insidious problems is the saturation of the hybridization signal of high-abundant transcripts. This problem arises from the truncation of the laser fluorescence signal. When the hybridization signal on the microarray is very strong, this truncation can result in serious consequences that may not be readily apparent to the user. As an illustration of this problem, two subclasses of normal human tissue samples (six liver and six lung samples) were analyzed with GeneChip probe arrays to evaluate the patterns of expression for approximately 7000 human genes. Five of these data sets were found to suffer from signal truncation. This caused several tissues to be incorrectly classified using hierarchical clustering. To rectify this problem so that the gene expression data could be properly compared and clustered, we developed a "filtering" procedure that identifies a subset of genes least affected by the signal saturation. This filtering procedure can be obtained at www.hugeindex.org.

Aged↗
PubMed2001

A compendium of gene expression in normal human tissues.

This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org) for future studies of pathophysiology.

Cluster Analysis↗
PubMed2001

Changes in contaminant levels in New Jersey osprey eggs and prey, 1989 to 1998.

Ospreys are good indicators of the health of estuarine areas because they feed almost exclusively on fish with the balance on other aquatic biota. Through the 1980s, ospreys nesting on Delaware Bay in New Jersey had reduced reproductive success relative to those nesting on the Atlantic coast and the Maurice River, a tributary of Delaware Bay. Earlier research suggested that elevated levels of DDT and polychlorinated biphenyl (PCB) contaminants identified in addled osprey eggs contributed to this reduced productivity. We repeated egg and prey sampling initially conducted in 1989 to evaluate the trends of contaminants in the last decade. Most organochlorine contaminants declined in osprey eggs in 1998 relative to 1989. Across three study areas, PCBs decreased from 4.1-7.7 ppm in 1989 to 1.8-3.2 ppm in 1998; DDE decreased from 1.2-3.2 ppm in 1989 to 0.7-1.2 ppm in 1998. Lead in eggs increased from an average of 0.01 to 0.30 ppm wet weight, and mercury averaged 0.12 ppm and increased only in Atlantic coast eggs. Most of these contaminant changes were also found in typical prey fish: PCBs decreased from 0.18-1.2 ppm in 1989 to 0.06-0.43 ppm in 1998; DDE decreased from 0.05-0.69 ppm in 1989 to 0.03-0.13 ppm in 1998. Lead and mercury increased in most fish samples. The improvement in most organochlorine contaminants in osprey eggs and prey reflected improved nest success in the Delaware Bay study area, and the nesting populations in the Atlantic and Maurice River study areas increased approximately 200% since 1989. PCBs and DDE in osprey eggs were below levels considered to be toxic to egg development. This study documents significant improvements in organochlorine contaminants in southern New Jersey ospreys, but justifies continued monitoring of heavy metals, such as lead and mercury, in aquatic ecosystems.

Animals↗
PubMed2001

Hemodynamic response to tibolone in reproductive and nonreproductive tissues in the sheep.

OBJECTIVE: We sought to determine the hemodynamic effects of tibolone in reproductive and nonreproductive tissues in the nonpregnant ovariectomized sheep. STUDY DESIGN: Six ewes were chronically instrumented for measurement of mean arterial pressure, heart rate, cardiac output, and coronary and uterine blood flow. A dose response curve was generated for intravenous tibolone (1.25, 2.5, and 5 mg) and compared with intravenous 17beta-estradiol (1 microg/kg body weight). To determine whether tibolone-related cardiovascular responses were estrogen receptor mediated and produced by nitric oxide, animals were treated on separate days with either estrogen receptor antagonist ICI 182,780 or the nitric oxide synthase inhibitor, L -nitroarginine methyl ester. RESULTS: Tibolone significantly increased coronary blood flow in a dose-related fashion by 5% +/- 3%, 9% +/- 2%, and 11% +/- 2% for the 1.25, 2.5, and 5 mg doses, respectively. Uterine blood flow was also increased significantly in a dose-dependent manner by 98 +/- 15, 216 +/- 59, and 303 +/- 56 mL/min, for the 1.25, 2.5, and 5 mg doses, respectively. L -Nitroarginine methyl ester attenuated tibolone-induced increases in uterine blood flow by 84% +/- 4% and abolished the increase in coronary blood flow. ICI 182,780 inhibited all tibolone-induced cardiovascular responses. CONCLUSION: Tibolone significantly increases coronary and uterine blood flow in ovariectomized ewes. The coronary and uterine vascular responses are mediated via an estrogen receptor-dependent mechanism and are produced mainly by nitric oxide.

Anabolic Agents↗
PubMed2001

Estrogen receptor beta is the predominant isoform expressed in the brain of adult and fetal sheep.

OBJECTIVE: The objective of this study was to examine the expression of estrogen receptors alpha and beta in the cerebral cortex of the adult and fetal sheep. STUDY DESIGN: A reverse transcriptase-polymerase chain reaction-based approach was used to examine the expression of ovine estrogen receptor alpha and estrogen receptor beta in the cerebral cortex of 4 adult and 2 fetal sheep. RESULTS: Estrogen receptor beta was expressed in the 4 adult and 2 fetal brain samples. Estrogen receptor alpha expression was seen in only 1 adult brain and 1 fetal brain. CONCLUSION: Estrogen receptor beta is the predominant isoform expressed in the cerebral cortex of both adult and fetal sheep. These data may have implications for the many important actions of estrogen in the adult and developing ovine brain.

Aging↗
PubMed2001

Leptin in the ovine fetus correlates with fetal and placental size.

OBJECTIVE: The purpose of this study was to detect the presence of leptin and its receptor in ovine fetal tissues and to examine the relationship between circulating leptin concentrations and fetal and placental weights on gestational day 138 (GD138) of ovine pregnancy (term, 145 days). STUDY DESIGN: Pregnant sheep (n = 18) were instrumented on GD 110 to facilitate measurement and chronic reduction of uterine blood flow and produce intrauterine growth restriction. Four animals that served as controls were euthanized on GD 138 to obtain fetal tissues to determine the presence of ovine leptin and its receptor by reverse transcriptase-polymerase chain reaction. Seven instrumented animals were randomized into the control group, and 7 instrumented animals were randomized into the uterine blood flow restricted group (reduction equaled approximately 50% on GD 138). Maternal and fetal blood samples were obtained on day 138 to measure plasma leptin concentrations, and animals were euthanized for the determination of fetal morphometrics and placental weight. RESULTS: Expression of RNA for ovine leptin and its receptor were observed in fetal liver, skeletal muscle, kidney, heart, and placenta. Fetal body weight, ponderal index, and placental weight were significantly decreased by approximately 40% in the blood flow restricted group as compared with controls. Fetal leptin concentrations were increased by 45% in the uteroplacental blood flow restricted group (P =.01). Maternal leptin concentrations were not significantly different between the 2 groups and did not correlate with fetal concentrations. Fetal leptin concentrations had an inverse relationship with uterine blood flow (r = -0.73; P =.004), fetal body weight (r = -0.78; P =.002), and placental weight (r = -0.68; P =.01). CONCLUSION: Ovine fetal tissues express RNA for leptin and its receptor. Circulating leptin concentrations in the ovine intrauterine growth restriction fetus were significantly elevated on gestational day 138 compared with controls. Fetal leptin concentrations were inversely related to uterine blood flow and fetal and placental weight. These findings suggest that fetal leptin may be involved in an adaptive response to intrauterine growth restriction.

Animals↗
PubMed2001

Mechanism of uterine vascular refractoriness to endothelin-1 in pregnant sheep.

Endothelin-1 (ET-1) is a potent vasoconstrictor and produces marked pressor responses when given systemically. Studies in sheep have demonstrated that during pregnancy the uterine vasculature is refractory to exogenously administered ET-1. We hypothesize that this pregnancy-dependent refractoriness is due to an upregulation of local uterine metabolism of ET-1 and/or ET(B) receptors and/or downregulation of local uterine ET(A) receptors. To investigate these possibilities, 21 nonpregnant and 17 pregnant sheep were used. Dose-response curves to intravenous infusion of ET-1 and phenylephrine were generated for pregnant and nonpregnant sheep. ET-1 infused systemically demonstrated vasoconstriction in the systemic and renal vasculature of pregnant and nonpregnant animals and vasoconstriction in the uterine vasculature of nonpregnant animals. The pregnant animals showed no uterine vascular response to ET-1. In contrast, phenylephrine showed vasoconstriction in the systemic, renal, and uterine circulations in both pregnant and nonpregnant sheep. After experimentation, the animals were euthanized, and tissues were harvested for Western blot and activity analysis of neutral endopeptidase (NEP) or RT-PCR analysis of endothelin-converting enzyme (ECE) and ET(A) and ET(B) receptors. The content and activity of NEP in the uterine and renal vasculature of pregnant and nonpregnant animals were similar. RT-PCR demonstrated the presence of ECE in the uterine vasculature of pregnant and nonpregnant sheep. ET(A) receptor mRNA was significantly reduced in pregnant compared with nonpregnant sheep, whereas ET(B) receptor mRNA remained unchanged. We conclude that the uterine vascular refractoriness seen in the pregnant sheep is due to a downregulation of ET(A) receptors.

Animals↗
PubMed2000

Coronary and uterine vascular responses to raloxifene in the sheep.

OBJECTIVE: We sought to determine whether raloxifene increases coronary and uterine blood flow in ovariectomized ewes. STUDY DESIGN: Twelve ewes were chronically instrumented for measurement of mean arterial pressure, heart rate, cardiac output, coronary blood flow, and uterine blood flow. Sheep received 17beta-estradiol, Estrace, raloxifene, or KY Jelly vehicle on separate days. RESULTS: 17beta-Estradiol increased uterine blood flow from 21 +/- 3 to 254 +/- 36 mL/min and coronary blood flow by 21% +/- 2% within 2 hours. Estrace increased uterine blood flow from 30 +/- 7 to 260 +/- 62 mL/min and coronary blood flow by 8% +/- 4% within 3 hours. Raloxifene increased uterine blood flow from 20 +/- 3 mL/min to 220 +/- 53 mL/min by 6 hours and coronary blood flow by 22% +/- 5% within 24 hours. To determine whether hemodynamic responses were mediated by nitric oxide, L -nitroarginine methyl ester was administered and produced an approximate 50% decrease in uterine blood flow for all 3 compounds. L -Nitroarginine methyl ester attenuated increases in coronary blood flow induced by 17beta-estradiol, Estrace, and raloxifene. CONCLUSION: Raloxifene has significant coronary and uterine vascular effects in the ovariectomized ewe. The coronary and uterine responses are partially mediated by nitric oxide.

Administration, Intravaginal↗
PubMed2000

Premarin-induced increases in coronary and uterine blood flow in nonpregnant sheep.

OBJECTIVE: Menopause is associated with an increased incidence of cardiovascular disease among women, and estrogen replacement therapy is thought to reduce the risk of coronary artery disease. The mechanism by which this occurs is unclear, but coronary arterial endothelial and vascular smooth muscle cells have been shown to contain estrogen receptors, and their stimulation appears to increase nitric oxide synthesis. One conjugated estrogen preparation (Premarin) is widely used in postmenopausal hormone replacement therapy, but little is known about its effects on cardiovascular hemodynamics. STUDY DESIGN: This study was designed to determine whether Premarin, like 17beta-estradiol, has significant effects on cardiac output and coronary and uterine blood flows at doses used clinically (0.625, 1.25, and 2.5 mg). Nonpregnant oophorectomized sheep were implanted with instruments to measure cardiac output, left coronary (circumflex) artery blood flow, uterine blood flow, heart rate, and systemic arterial blood pressure. After recovery from surgery, the animals received intravenous bolus injections of either 17beta-estradiol (1.0 microg/kg), Premarin (0.625, 1.25, or 2. 5 mg), or vehicle on different days. RESULTS: The 1.0-microg/kg dose of 17beta-estradiol significantly increased coronary blood flow by 15% +/- 2% from baseline (mean +/- SEM). Premarin also increased coronary blood flow significantly at the 1.25- and 2.5-mg dose levels by 12% +/- 3% and 14% +/- 4%, respectively. As expected 17beta-estradiol increased uterine blood flow from a baseline of 15 +/- 3 mL/min to 169 +/- 19 mL/min. Premarin treatment was associated with a significant increase in uterine blood flow, which increased from an average baseline of 14 +/- 4 mL/min to 46 +/- 10 mL/min, 95 +/- 18 mL/min, and 135 +/- 20 mL/min at the three doses tested (0. 625, 1.25, and 2.5 mg, respectively). 17beta-Estradiol also increased cardiac output by 12% +/- 3%. Premarin increased cardiac output 2% +/- 3%, 9% +/- 4%, and 11% +/- 3%, with only the highest dose producing a significant change. 17beta-Estradiol also increased heart rate by 12% +/- 1%, whereas Premarin at doses of 0.625, 1.25, and 2.5 mg increased it by 4% +/- 3%, 7% +/- 4%, and 10% +/- 2%, respectively (increase significant only at the highest dose). Neither 17beta-estradiol nor Premarin altered either stroke volume or systemic arterial pressure. CONCLUSION: Premarin, like 17beta-estradiol, has significant systemic, coronary, and uterine vascular effects. These vascular effects may help to explain in part why these compounds are cardioprotective.

Animals↗
PubMed2000

The role of nitric oxide in mediating adenosine-induced increases in uterine blood flow in the oophorectomized nonpregnant sheep.

OBJECTIVE: Adenosine administration to the uterine vasculature of the nonpregnant oophorectomized sheep results in dose-related increases in uterine blood flow. This study was designed to determine whether these adenosine-induced increases in uterine blood flow are mediated in part by nitric oxide release. STUDY DESIGN: Five nonpregnant oophorectomized ewes had catheters placed in the femoral artery and vein and in the lateral branches of the right and left main uterine arteries. Adenosine dissolved in isotonic sodium chloride solution was infused into the uterine artery at sequentially increasing doses (1, 3, 10, 30, 100, and 300 microg/min), and a dose-response curve was constructed. After determination of control responses to adenosine a 10-mg/kg dose of the nitric oxide synthase inhibitor N omega-nitro-L -arginine methyl ester was administered into the femoral vein; the dose-response curves to adenosine were then determined again. Responses after N omega-nitro-L -arginine methyl ester administration were compared with those obtained before nitric oxide blockade. RESULTS: Adenosine increased uterine blood flow in a dose-related fashion, from a baseline of 11 +/- 2 mL/min to 140 +/- 19 mL/min. No further increase was seen with adenosine doses >300 microg/min. There were no significant alterations in systemic arterial pressure or heart rate in response to uterine infusion of adenosine. N omega-nitro-L -arginine methyl ester administration increased baseline blood pressure 24% +/- 4% and decreased heart rate 13% +/- 4%. Responses to adenosine after N omega-nitro-L -arginine methyl ester administration were significantly reduced, from a maximum at the highest dose of 140 +/- 19 mL/min to 95 +/- 13 mL/min (P <.001). CONCLUSION: A significant portion of adenosine-induced vasodilation in the uterine vasculature appears to be mediated by the release of nitric oxide.

Adenosine↗
PubMed2000

Functional role of angiotensin II type 1 and 2 receptors in regulation of uterine blood flow in nonpregnant sheep.

The objective was to determine the receptor subtype of angiotensin II (ANG II) that is responsible for vasoconstriction in the nonpregnant ovine uterine and systemic vasculatures. Seven nonpregnant estrogenized ewes with indwelling uterine artery catheters and flow probes received bolus injections (0.1, 0.3 and 1 microg) of ANG II locally into the uterine artery followed by a systemic infusion of ANG II at 100 ng x kg(-1) x min(-1) for 10 min to determine uterine vasoconstrictor responses. Uterine ANG II dose-response curves were repeated following administration of the ANG II type 2 receptor (AT(2)) antagonist PD-123319 and then repeated again in the presence of an ANG II type 1 receptor (AT(1)) antagonist L-158809. In a second experiment, designed to investigate the mechanism of ANG II potentiation that occurred in the presence of AT(2) blockade, nonestrogenized sheep received a uterine artery infusion of L-158809 (3 mg/min for 5 min) prior to the infusion of 0.03 microg/min of ANG II for 10 min. ANG II produced dose-dependent decreases in uterine blood flow (P < 0.03), which were potentiated in the presence of the AT(2) antagonist (P < 0.02). Addition of the AT(1) antagonist abolished the uterine vascular responses and blocked ANG II-induced increases in systemic arterial pressure (P < 0.01). Significant uterine vasodilation (P < 0.01) was noted with AT(1) blockade in the second experiment, which was reversed by administration of the AT(2) antagonist or by the nitric oxide synthetase inhibitor N(omega)-nitro-L-arginine methyl ester. We conclude that the AT(1)-receptors mediate the systemic and uterine vasoconstrictor responses to ANG II in the nonpregnant ewe. AT(2)-receptor blockade resulted in a potentiation of the uterine vasoconstrictor response to ANG II, suggesting that the AT(2)-receptor subtype may modulate uterine vascular responses to ANG II potentially by release of nitric oxide.

Angiotensin II↗
PubMed2000

Effects of chronic reduction in uterine blood flow on fetal and placental growth in the sheep.

Pregnancy is associated with a significant increase in uteroplacental blood flow (UBF), which is responsible for delivering adequate nutrients and oxygen for fetal and placental growth. The present study was designed to determine the effects of vascular insufficiency on fetal and placental growth. Thirty-nine late-term pregnant ewes were instrumented to investigate the effects of chronic UBF reduction. Animals were split into three groups based on uterine blood flow, and all animals were killed on gestational day 138. UBF, which began at 851 +/- 74 ml/min (n = 39), increased in controls (C) to 1,409 +/- 98 ml/min (day 138 of gestation) and in the moderately restricted (R(M)) group to 986 +/- 69 ml/min. In the severely restricted (R(S)) group, UBF was only 779 +/- 79 ml/min on gestational day 138. This reduction in UBF significantly affected fetal body weight with R(M) fetuses weighing 3,685 +/- 178 g and R(S) fetuses weighing 2,920 +/- 164 g compared with C fetal weights of 4,318 +/- 208 g. Fetal brain weight was not affected, whereas ponderal index was significantly reduced in R(M) (2.94 +/- 0.09) and R(S) fetuses (2.49 +/- 0.08) compared with the value of the C fetuses (3.31 +/- 0.08). Placental weight was also significantly reduced in the R(M) group, being 302 +/- 24 g, whereas the R(S) group placenta weighed 274 +/- 61 g compared with the C values of 414 +/- 57 g. Fetal heart, liver, lung, and thymus were all significantly smaller in the R(S) group. Thus the present study shows a clear relationship between the level of UBF and both fetal and placental size. Furthermore, the observation that fetal brain weight was not affected, whereas fetal body weight was significantly reduced suggests that this experimental preparation may provide a useful model in which to study asymmetric fetal growth restriction.

Animals↗
PubMed2000

Connectedness and autonomy support in parent-child relationships: links to children's socioemotional orientation and peer relationships.

Connectedness and autonomy support in the parent-child relationship are constructs that emerge from object relations and attachment theories but that overlap with other commonly studied qualities of parent-child relationships to provide a unifying focus for research in this domain. In this study, these constructs were examined in relation to children's relational competence, including socioemotional orientation, friendship, and peer acceptance. Semistructured conversations between mothers and their 5-year-olds (N = 192) were videotaped at home and rated for (a) connectedness between the members of the dyad and (b) the parent' s support for the child's autonomy. Results showed that connectedness was correlated with children's socioemotional orientations, number of mutual friendships, and peer acceptance and that the relation between parent-child connectedness and children's peer relationships was mediated by children's prosocial-empathic orientation. Implications of these findings for theories that link parent-child relationships to the development of relational competence in children are discussed.

Adult↗
PubMed1999

Hemodynamic effects of platelet-activating factor in nonpregnant and pregnant sheep.

The present study was designed to assess the dose-related effects of platelet-activating factor (PAF) on systemic, renal, and uterine hemodynamics in nonpregnant sheep and to evaluate how pregnancy might alter these responses. Nonpregnant and pregnant (110 +/- 5 days gestation) ewes were instrumented for conscious measurements of maternal mean arterial pressure (MAP), renal blood flow (RBF), uterine blood flow (UBF), hematocrit, and urinary protein concentration. After recovery, dose-response curves to PAF were generated by systemic infusion at 10, 30, and 100 ng. kg(-1). min(-1) (15 min/dose) into the maternal femoral vein. The above parameters were measured, and renal and uterine vascular resistances (RVR and UVR, respectively) were calculated. In pregnant sheep, PAF increased MAP, RVR, UVR, and urinary protein concentration. We also observed increases in hematocrit, indicative of reduced blood volume secondary to increased systemic microvascular protein permeability. These responses were similar in nonpregnant sheep, with the exception of UVR in nonpregnant ewes being decreased (and thus UBF was increased), whereas in pregnant sheep, UVR was increased, which resulted in decreased UBF. This suggests that pregnancy alters the mechanism of action of PAF within the uterine vasculature in a way that can reduce UBF and thereby potentially compromise placental perfusion.

Animals↗
PubMed1997

A comparison of mercury levels in feathers and eggs of osprey (Pandion haliaetus) in the North American Great Lakes.

Osprey (Pandion haliaetus) eggs and chick feathers were collected for mercury analysis from nests at four Great Lakes study areas in Ontario (three "naturally formed" lakes in southern Ontario and one reservoir in northern Ontario) and two New Jersey study areas in 1991-1994. Adult osprey feathers were sampled from three Great Lakes study areas in 1991. Feathers sampled from chicks (approximately 28-35 days old) appear to be better indicators of local contaminant conditions since spatial patterns of mercury in known prey, yellow perch (Perca flavescens), also collected in these areas, were more similar to chick feathers than to eggs. Mercury levels were less variable in chick feathers than in eggs. Estimates of biomagnification factors using prey of known size at these areas were also less variable in feathers than in eggs. At naturally formed lakes, no significant correlation in mercury levels between eggs and chick feathers from the same nest was apparent, suggesting that the source of mercury contamination was not the same in these two tissues: mercury levels in eggs reflect mercury acquired on the breeding grounds, wintering grounds, and migratory route; mercury levels in chick feathers reflect local dietary conditions on the breeding grounds. Mercury levels in both osprey eggs and chick feathers were higher at the Ogoki Reservoir than at naturally formed lakes. Adult osprey feathers had higher mercury concentrations than chick feathers. Mercury levels in osprey eggs, chick feathers, and adult feathers did not approach levels associated with toxic reproductive effects.

Animals↗
PubMed1997

Estrogen-induced increases in coronary blood flow are antagonized by inhibitors of nitric oxide synthesis.

OBJECTIVE: Estrogen receptors have been found in coronary arterial endothelial and vascular smooth muscle cells. Therefore the present study was designed to determine if estradiol-17 beta can increase coronary blood flow and if so whether the changes are mediated by nitric oxide. STUDY DESIGN: Five oophorectomized non-pregnant sheep were chronically instrumented to measure blood pressure, heart rate, cardiac output, left circumflex coronary blood flow and central venous pressure. Animals received estradiol-17 beta (1.0 micrograms/kg) and cardiovascular responses were followed for 135 min. RESULTS: Estradiol-17 beta (1.0 micrograms/kg) increased left circumflex (coronary) blood flow 28 +/- 3%, cardiac output 15 +/- 1% and heart rate by 13 +/- 3%. Coronary vascular resistance decreased 23 +/- 5%, systemic vascular resistance decreased by 12 +/- 2% while blood pressure did not change significantly. Administration of the nitric oxide synthetase inhibitor L-nitroarginine methylester (L-NAME), had no effect on basal coronary blood flow but completely reversed estradiol-17 beta induced increases in coronary blood flow. CONCLUSION: These results demonstrate that estrogen increases coronary blood flow in the non-pregnant sheep and that L-NAME, an inhibitor of nitric oxide, is able to reverse the estrogen induced flow changes.

Animals↗