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PubMed1990

Acute effects of doxazosin and atenolol on smoking-induced peripheral vasoconstriction in hypertensive habitual smokers.

The acute effects of selective alpha 1 inhibition with doxazosin (0.5-0.7 mg intravenously) and beta 1-blockade with atenolol (0.1 mg/kg body weight, intravenously) on smoking-induced peripheral vasoconstriction were investigated in 24 hypertensive habitual smokers. Forearm blood flow was measured by venous occlusion plethysmography and skin blood flow was estimated by thermography and laser doppler flowmetry. After the patients had smoked two cigarettes, plasma adrenaline elevations were similar under basal conditions and after drug administration; plasma noradrenaline remained unchanged. The smoking-induced increase in the heart rate was attenuated by atenolol compared with basal values. The smoking-induced increase in systolic blood pressure was more marked after atenolol and doxazosin (P less than 0.05) than before the drug administration. The smoking-induced increase in diastolic blood pressure was enhanced by atenolol (P less than 0.05) but unchanged by doxazosin. Smoking increased forearm vascular resistance under basal conditions (P less than 0.05) and after atenolol (P less than 0.01) but not after doxazosin. Similarly, skin temperature was significantly reduced by smoking under basal conditions and after the administration of atenolol (P less than 0.001) but not doxazosin. The smoking-induced reduction in skin blood flow was attenuated by doxazosin compared with atenolol (P less than 0.05). Thus, smoking-induced muscular and cutaneous vasoconstriction was inhibited by doxazosin as opposed to atenolol in hypertensive habitual smokers. This may reflect unmasked beta-adrenoceptor mediated vasodilation in addition to attenuated alpha 1-adrenoceptor mediated vasoconstriction.

Adrenergic alpha-Antagonists↗
PubMed1986

Starvation-induced changes in metabolic rate, blood flow, and regional energy expenditure in rats.

Starvation results in an energy-conserving reduction in metabolic rate that has features of an adaptive response. Tissue and organ sites of this response were investigated by examining the effects of starvation for 5 d on tissue blood flow (microsphere method) and regional arteriovenous O2 differences ((a-v)O2) in conscious rats resting quietly at 28 degrees C. Comparison was with fed and overnight-fasted animals. Whole body resting metabolic rates (MR), colonic temperatures (Tc), and tissue weights were also determined. Quantitative changes in energy expenditure (as O2 consumption) were obtained for two regions: the portal-drained viscera (PDV) and the hindquarters (HQ). Fasting overnight resulted in increased blood flow to white adipose tissue (WAT) and decreased flow to the brain, PDV, testes, and skin; however, MR, Tc, the two regional ((a-v)O2, and the weights of most tissues were not significantly altered. In comparison with overnight fasting, starvation for 5 d resulted in a 13% reduction in body weight, weight loss in many tissues and organs, a 26% reduction in MR, a decline of 0.5 degree C in Tc, decreased (a-v)O2 across both the PDV and HQ, reduced cardiac output, and decreased blood flow to the heart, PDV, skin, WAT, leg muscle, HQ, and the musculoskeletal body as a whole. Utilization of O2 by the PDV and HQ (flow X (a-v)O2) declined by amounts that accounted for 22 and 18%, respectively, of the reduction in MR. The reductions in cardiac output (18%) and heart blood flow (36%) indicate that the heart also made a contribution to energy conservation (roughly estimated as 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Self-palpation to assess cervical changes in relation to mucus and temperature.

Women experienced in cervical self-palpation recognize fertile characteristics when the cervix is high, open, soft, and straight; this happens under estrogenic influence. The cervix is said to show infertile signs when it is low, closed, firm, and lying against the vaginal wall; that change occurs quickly under progesterone influence. The objective of this study was to assess the time relationship among changes in the cervix observed by self-palpation, changes in cervical mucus as observed by women, and the shift in basal body temperature during ordinary cycles. A total of 215 symptothermal charts from natural family planning users were analyzed. The duration of the change from the maximum fertility characteristics to the postovulatory return to definite signs of infertility was measured. This duration ranged from 1 to 7 days, with a mean of 2.65. The timing of maximum fertility signs in the mucus was compared with that of maximum fertility signs in the cervix: it varied from 3 days before to 6 days after, with a mean of 0.48 day. The timing of the first high temperature was compared with that of return to definitely infertile characteristics: it varied from 6 days before to 3 days after, with a mean of -0.69 day. Some of the variation may be due to the presence of inexperienced users in the sample. However, a mean difference of half a day between the most fertile cervix and the most fertile mucus on one hand and between the first day of infertile cervix and the first high temperature on the other hand suggest that the cervical changes could be useful indicators of estrogen and progesterone actions.

Adult↗
PubMed2003

Resting energy metabolism of Goeldi's monkey (Callimico goeldii) is similar to that of other callitrichids.

The resting metabolic rates (RMRs) of six adult Goeldi's monkeys (Callimico goeldii) were measured using standard methods of open circuit respirometry during both the active (daytime) and inactive (nighttime) circadian phases for this species. One subject was measured both while she was pregnant and after she delivered a full-term, stillborn infant. Inactive-phase RMR within thermal neutrality (above 27.5 degrees C) averaged 288.5 +/- 30.8 ml O2/hr; active-phase RMR within thermal neutrality averaged 416.3 +/- 60.9 ml O2/hr. These values are 74.6% and 107.6%, respectively, of the mammalian expected for animals of this body mass. During the inactive phase, metabolic rate increased an estimated 4.3% for every degree decline in temperature below 27.5 degrees C. The RMR in Goeldi's monkey is similar quantitatively and qualitatively to those of other captive callitrichids that have been studied, with active-phase RMR being at or slightly above the mammalian expected, and inactive-phase RMR being significantly reduced. We propose that this circadian pattern of RMR is a consequence of small body size, and is not a specific metabolic adaptation within the Callitrichidae. Thus we predict that metabolic studies measuring both circadian phases in other small primates will also find this pattern of reduced RMR during the inactive phase. The inactive-phase RMR within thermal neutrality of the pregnant female was not different from that measured after the stillbirth, despite an almost 15% difference in body mass. During pregnancy, however, the female was more metabolically responsive to temperature below thermal neutrality, and had a lower upper critical temperature (i.e., was less tolerant of heat).

Animals↗
PubMed2003

Body size as a latent variable in a structural equation model: thermal acclimation and energetics of the leaf-eared mouse.

Body size is one of the most important determinants of energy metabolism in mammals. However, the usual physiological variables measured to characterize energy metabolism and heat dissipation in endotherms are strongly affected by thermal acclimation, and are also correlated among themselves. In addition to choosing the appropriate measurement of body size, these problems create additional complications when analyzing the relationships among physiological variables such as basal metabolism, non-shivering thermogenesis, thermoregulatory maximum metabolic rate and minimum thermal conductance, body size dependence, and the effect of thermal acclimation on them. We measured these variables in Phyllotis darwini, a murid rodent from central Chile, under conditions of warm and cold acclimation. In addition to standard statistical analyses to determine the effect of thermal acclimation on each variable and the body-mass-controlled correlation among them, we performed a Structural Equation Modeling analysis to evaluate the effects of three different measurements of body size (body mass, m(b); body length, L(b) and foot length, L(f)) on energy metabolism and thermal conductance. We found that thermal acclimation changed the correlation among physiological variables. Only cold-acclimated animals supported our a priori path models, and m(b) appeared to be the best descriptor of body size (compared with L(b) and L(f)) when dealing with energy metabolism and thermal conductance. However, while m(b) appeared to be the strongest determinant of energy metabolism, there was an important and significant contribution of L(b) (but not L(f)) to thermal conductance. This study demonstrates how additional information can be drawn from physiological ecology and general organismal studies by applying Structural Equation Modeling when multiple variables are measured in the same individuals.

Acclimatization↗
PubMedDate not supplied

Cortisol, hunger, and desire to binge eat following a cold stress test in obese women with binge eating disorder.

OBJECTIVE: Increased basal cortisol levels have been found in bulimia nervosa. After stress, increased cortisol levels have been associated with increased food intake in healthy women. Therefore, we assessed cortisol, hunger, and desire to binge eat after a cold pressor test (CPT) among women with binge eating disorder (BED). METHODS: Twenty-two obese (body mass index [BMI] = 36.7 +/- 6.5 SD) females (11 non-BED, 11 BED) completed the Zung depression scale and underwent the CPT, hand submerged in ice water for 2 minutes. Over 60 minutes, periodic ratings of hunger and desire to binge eat were obtained, just before blood draws for cortisol, as well as insulin. On a separate day, participants had a 1-mg oral dexamethasone suppression test (DST). RESULTS: The BED group had higher depression scores than the non-BED (p = .04), but depression was not a significant covariate for the cortisol response or to DST. After controlling for contraceptive use (n = 3), the BED group had higher basal cortisol than the non-BED group (p = .03), but cortisol did not differ after DST (p = .40). The BED group had nearly significant greater cortisol AUC after the CPT (p = .057) after controlling for insulin AUC and contraceptive use (p = .057). The BED group also had greater AUC for hunger (p = .03) and desire to binge eat (p = .02) after the CPT. CONCLUSION: These findings support our hypothesis of a hyperactive HPA-axis in BED, which may contribute to greater hunger and binge eating.

Adult↗
PubMed2002

The effects of gender and gonadal steroids on the neuroendocrine and temperature response to m-chlorophenylpiperazine in leuprolide-induced hypogonadism in women and men.

Studies of the effects of gender and gonadal steroids on serotonergic activity in humans are few in number and often contradictory. We examined the neuroendocrine and core temperature response to a serotonergic stimulus, m-chlorophenylpiperazine (m-CPP) (0.08 mg/kg body weight, IV), in asymptomatic female and male volunteers during induced hypogonadism (leuprolide acetate) and hormone replacement (estradiol (E2) or progesterone (P4) in women; testosterone (T) in men). Compared with the hypogonadal state, basal prolactin (PRL) secretion was significantly higher during both P4 and E2 replacement (p <.05) in women and during T replacement in men (p <.05). m-CPP stimulated PRL secretion was significantly greater only during P4 (p <.05) but not E2 (women) or T (men) replacement, compared with hypogonadism. Basal but not stimulated plasma growth hormone (GH) levels were significantly higher during P4 in women and T in men (p <.05), and no significant differences in basal or m-CPP stimulated plasma levels of ACTH or cortisol were observed. Finally, basal core temperatures were significantly higher during P4 replacement compared with either E2 replacement or the hypogonadal condition (p <.01) in women, with no differences observed in men. Comparisons of measures by gender (and matched for baseline plasma T levels) revealed that during the hypogonadal state m-CPP-stimulated GH secretion was significantly greater (p <.01) and m-CPP-stimulated ACTH (p <.05) and cortisol (p <.01) significantly less in women compared with men. Although our data are limited to those components of the central serotonergic system influenced by m-CPP administration, our findings suggest the following: the regulatory effects of gonadal steroids on serotonergic function are modest in humans during leuprolide-induced hypogonadism; menstrual cycle phase effects of serotonergic agents on PRL secretion may reflect both the effects of P4 and E2; the effects of P4 in humans may occur without E2 priming of the progesterone receptor; and gender differences in GH secretion occur independent of the presence of gonadal steroids.

Adult↗
PubMed2000

The role of beta-adrenergic receptors in the cutaneous water evaporation mechanism in the heat-acclimated pigeon (Columba livia).

The effects of selective and non-selective beta-adrenergic agents on cutaneous water evaporation (CWE) were studied in hand-reared rock pigeons (Columba livia). CWE was measured by the vapor diffusive resistance method, using a transient porometer. Intramuscular and subcutaneous injections of a non-selective beta-adrenergic antagonist (propranolol) or a selective beta(2)-adrenergic antagonist (ICI-118551) to heat-acclimated (HAc) pigeons at ambient temperature (T(a)) of 24 degrees C resulted in intensive CWE. The CWE values that were triggered by propranolol and ICI-118551 (18.59+/-0.73 and 16.48+/-0.70 mg cm(-2) h(-1), respectively) were close to those induced by heat exposure (17.62+/-1.40 mg cm(-2) h(-1)). Subcutaneous administration of propranolol produced local response. Intramuscular injection of salbutamol (selective beta(2)-adrenergic agonist) to HAc pigeons drastically diminished CWE induced by either propranolol, metoprolol or heat exposure. Such manipulations also enhanced panting at relatively low T(a)s (42 degrees C). The inhibition of beta(1)-adrenergic receptors by metoprolol increased CWE, while inhibition by atenolol produced no change from basal values. This difference may be attributed to their distinctive nature in penetrating the blood-brain barrier. Our findings indicate a regulatory pathway for CWE consisting of both beta(1)- and beta(2)-adrenergic receptors. We suggest that the beta(1)-adrenergic effect is restricted mainly to the CNS, while the beta(2)-adrenergic effect takes place at the effector level. We postulate this level to be either the cutaneous microvasculature or the epidermal layer.

Acclimatization↗
PubMed1999

Transmission electron microscopy findings in the respiratory epithelium of guinea pigs exposed to the polluted air of southwest Mexico City.

We evaluated the nature and the extent of the damage to the respiratory epithelium of guinea pigs after a 4-month exposure to the mixture of air pollutants in southwest Mexico City. Guinea pigs were placed outdoors on the roof of our facility, 8 hours daily, from February to May 1995. At the same time, control guinea pigs were kept indoors breathing filtered air. Air pollutants, temperature, and humidity data were obtained from the nearest station of the Environmental Monitoring Net. The airways and lung parenchyma were analyzed after 120 days using transmission electron microscopy (TEM). During the 4-month exposure period, ozone (O3) exceeded the norm during 511 hours, and suspended particles less than 10 microm in diameter (PM10) during 52 hours. Both pollutants reached peak levels of more than twice the norm. TEM revealed no important abnormalities in the control group. In the exposed group, there was loss of cilia, detachment of epithelial cells, and eosinophil and macrophage migration toward alveolar spaces through type I pneumocytes with destruction of their basal membranes. In six guinea pigs in the exposed group, we noted bacteria along the airways, with associated inflammatory response. We explain the colonization of the respiratory epithelium by bacteria as the result of the impairment on the defense mechanism caused by the exposure to environmental O3 and PM10.

Air Pollutants↗
PubMed2007

Skin tissue water and laser Doppler blood flow during a menstrual cycle.

Previous work offers conflicting evidence concerning whether basal skin blood flow (SBF) varies with the menstrual cycle. Our goal was to determine the extent of cycle-dependent changes in forearm SBF parameters and if they are linked to local tissue water content and arm volume changes. Both arms of 10 premenopausal women were evaluated three times during their cycle (days 4, 12 and 22) and 10 postmenopausal women were evaluated once. Each evaluation included laser Doppler blood flow parameters (perfusion, volume and velocity), skin temperature, arm volume and local tissue water determined by a new tissue dielectric constant method. Estradiol and progesterone concentrations were determined at each visit by using saliva samples and analysis showed the expected pattern of variation over the cycle. Main results showed no significant cycle-dependent variations in any SBF parameter, temperature, tissue water or arm volume. Postmenopausal women had significantly less estradiol levels, but did not differ with respect to premenopausal women in any measured parameter except for a slightly less blood velocity (P<0.01). We hypothesize that that the absence of changes in tissue water and arm volume in our group may account for the constancy of the measured SBF parameters. However, in other populations, hormonally induced tissue changes may occur and contribute to the cycle-dependent changes in resting blood perfusion that have been reported. This possibility suggests that it may be useful to measure and report a skin tissue water index when serial changes in blood perfusion are being investigated.

Adult↗
PubMed2005

Acute and long-term effects of winter swimming and whole-body cryotherapy on plasma antioxidative capacity in healthy women.

The effects of severe cold stress on total peroxyl radical trapping antioxidant capacity of plasma (TRAP) were studied in two groups of healthy women: a whole-body cryotherapy group (WBC, n = 10) and a winter swimming group (WS, n = 10). The biovariability of TRAP values was also analysed. The WBC group was exposed to -110 degrees C for 2 min, whereas the exposure for the WS group lasted 20 s in ice-cold water. Sessions were organized three times per week for 12 weeks. Blood specimens were collected at 2, 4, 8 and 12 weeks at rest, 2 and 35 min after the cold exposures and at the corresponding times without cold exposure on a separate day. Conventional methods were used to determine TRAP values. The between-subject variation was 13.6% and the within-subject variation 6.4%. The index of individuality was 0.46, and the index of heterogeneity was 0.079. These results indicate a marked heterogeneity among subjects. During the first 4 weeks, the mean TRAP value significantly increased at 2 min after cold exposure in the WBC group, returning to baseline 35 min after the exposure. Similar changes were observed in the WS group. However, all changes due to cold were relatively mild (<5%). After 4 weeks no changes in TRAP values after the cold exposures were noticed and no long-term changes in basal TRAP values were observed. In the main, regular WBC and WS do not seem to be harmful as far as plasma antioxidative capacity is concerned.

Adult↗
PubMed1995

Deep hypothermia diminishes the ischemic induction of heat-shock protein-72 mRNA in piglet brain.

BACKGROUND AND PURPOSE: Expression of the 72-kD heat-shock protein (HSP72) has served as a useful indicator of ischemic stress after cerebral ischemia. Moderate hypothermia (30 degrees C) has been reported to block the induction of HSP72 after a brief episode of forebrain ischemia. The objective of the present study was to examine the effects of deep hypothermia (15 degrees C) on expression of HSP72 after a prolonged period of cerebral ischemia. METHODS: Piglets 19 to 23 days old, were placed on cardiopulmonary bypass, and brain temperature was lowered to 23 degrees C (n = 9) or 15 degrees C (n = 9) before circulatory arrest for 1 hour. In an additional group of animals (n = 5), the temperature was lowered to 29 degrees C before arrest for 45 minutes. All animals were reperfused at 37 degrees C for 2 hours, and the regional expression of HSP72 mRNA was assessed using in situ hybridization. RESULTS: After ischemia at 15 degrees C, expression of HSP72 mRNA was limited to a few scattered regions of cerebral cortex; the percentage of cortex exhibiting HSP72 mRNA was 23 +/- 7% (mean +/- SEM). Ischemia at 23 degrees C triggered expression of HSP72 mRNA in a significantly larger portion of the cortex (68 +/- 8%, P < .001). Ischemia at 29 degrees C failed to induce substantial expression of HSP72 mRNA in the cerebral cortex. CONCLUSIONS: These results suggest that, relative to ischemia at 23 degrees C, deep hypothermia (15 degrees C) diminishes ischemic alterations leading to induction of HSP72 mRNA. The lack of cortical expression of HSP72 mRNA following ischemia at 29 degrees C may be secondary to inadequate recovery of energy metabolism.

Animals↗
PubMed2002

Modulation of sensory inputs and ectopic presence of Schwann cells depend upon the route and duration of nerve growth factor administration.

Nerve growth factor (NGF) ameliorates deficits in models of cholinergic hypofunction. However, notable adverse effects of intracerebroventricular (ICV) infusion of NGF include weight loss, Schwann cell hyperplasia (SCH), and aberrant sensory and sympathetic sprouting. In order to maintain efficacy on the cholinergic basal forebrain (CBF) and minimize these detrimental effects, intraparenchymal NGF infusion was compared with ICV administration to assess morphological and functional measures. NGF was delivered intraparenchymally (Intra-NGF) or intracerebroventricularly (ICV-NGF) for 3 and 6 months. Hypertrophy of cholinergic nucleus basalis neurons at 3 and 6 months was not different between both routes of administration, indicating similar efficacy for the CBF. SCH surrounding the medulla was observed in both Intra- and ICV-NGF animals due to the widespread distribution of NGF from the infusion site. The thickness of SCH reached a plateau at 3 months in ICV-NGF animals, while further proliferation occurred in Intra-NGF animals. More importantly, ectopic Schwann cells and aberrant sensory and sympathetic sprouting within the medulla oblongata were found solely in ICV-NGF animals. Differential changes in sensory processing were evident by an exaggerated response to acoustic stimuli in Intra-NGF animals and a decrease in thermal pain threshold in ICV-NGF-treated animals. Intra-NGF treatment did not produce the reduction in body weight exhibited by ICV-NGF-treated rats. These results indicate that different routes of NGF administration are identically efficacious for CBF neurons, but differentially modulate behaviors and structures leading to distinct profiles of adverse effects. Thus, current trophic factor delivery methods require further refinement to abolish detrimental effects.

Adrenergic Fibers↗
PubMed1984

Local cerebral metabolic effects induced by nigral stimulation following ventromedial thalamic lesions. I: Basal ganglia and related motor structures.

The effects of unilateral electrical stimulation of the substantia nigra (SN) were mapped in the extrapyramidal system of conscious rats bearing ventromedial thalamic (VM) lesions, using the quantitative autoradiographic 14C-deoxyglucose method. SN-stimulation in VM-intact rats resulted in metabolic activation within the deep layer of superior colliculus, subthalamic nucleus, ventrolateral thalamus and sensory-motor cortex ipsilaterally, and bilaterally in the reticulata, compacta, centrolateral and ventromedial thalamus, striatum, globus pallidus and entopeduncular nucleus. SN-stimulation 8 days following ipsilateral VM-lesion, induced activation only within the ipsilateral compacta, subthalamic and entopeduncular nuclei and the globus pallidus and in addition, the reticulata bilaterally. However, SN-stimulation 30 days following VM-injury elicited bilateral metabolic activation in all the examined structures. It is concluded that the VM-thalamic nucleus mediates information from one SN to the ipsilateral motor cortex and striatum, as well as to the extrapyramidal components of the contralateral hemisphere. Moreover, due to the plasticity of the central nervous system, one month following the VM-lesion transmission of information from the SN to all the bilateral components of this network is reestablished.

Animals↗
PubMed2001

No evidence for participation of non-adrenergic non-cholinergic subtances in brain death-related hemodynamic deterioration of the feline potential heart donor.

OBJECTIVE: To onset of brain death (BD) is associated with a hyperdynamic cardiovascular response caused by the acute sympathetic release of catecholamines. This is followed by progressive hemodynamic deterioration which may preclude heart donation for transplantation. The mechanism of the hemodynamic collapse is not fully understood. Changes in plasma concentrations of non-adrenergic non-cholinergic (NANC) substances, neuropeptide-Y (NP-Y, a vasoconstrictor) and the vasodilators calcitonin gene-related peptide (CGRP) and substance P (SP), were studied in relation to BD-related hemodynamic alterations. MATERIALS AND METHODS: Cats (6 BD and 6 controls (C)) were studied for 6 h. Heart rate (HR) and mean arterial pressure (MAP) were monitored. BD was induced at t = O min. At t = -5, 15, 60, 180 and 360 min, 5 ml arterial blood samples were taken. The plasma was collected and analyzed. The correlations between MAP and NANC levels were calculated. RESULTS: In the BD cats a maximal and significant increase in HR and MAP was observed at t = 2 min. HR returned to basal levels at t = 20 min and remained at that level. However, MAP deteriorated progressively to 53 +/- 8 mmHg (p 0.001 vs C) at/ = 360 min. NP-Y had increased from 59.7 +/- 2.5 to 110 +/- 20.2 pmol/l (p 0.05 vs C) at t = 15 min, had returned to basal value at t = 60 min and remained at that level. CGRP levels were lower and SP levels did not change vs C but both showed a trend towards higher levels at t = 360 min. The correlations between MAP and NP-Y, CGRP and SP appeared to be not significant. CONCLUSION: No evidence for participation of NANC substances could be demonstrated in brain death-related hemodynamic deterioration of the feline potential heart donor.

Animals↗
PubMed1989

Interobserver variation in estimation of day of conception intercourse using selected natural family planning charts.

In order to study outcome of pregnancy related to timing of conception it is necessary to have both markers of ovulation and records of intercourse. Natural family planning (NFP) charts where the woman records basal body temperature (BBT) and mucus signs are ideal for this purpose. Much work has been done relating timing of BBT and mucus signs to ovulation, but very little work has been done to examine interobserver agreement on the interpretation of these signs. Four NFP experts examined 28 NFP pregnancy charts to determine the BBT rise, the mucus peak, and two most likely days of conception intercourse. The charts were selected because they provided difficulties in interpretation. The reviewers were able to agree on the most probable day of conception intercourse in 96.4% of cases, on the mucus peak in 74.1% of cases, and on the interval between the most probable conception intercourse and mucus peak in 70.4% of cases. There was poor agreement on the first day of the BBT rise (38.5%). The authors conclude that in selected difficult NFP charts, the mucus peak is a more valid indirect measure of ovulation both because it is subject to less interobserver variation and because it more closely approximates the timing of ovulation.

Body Temperature↗
PubMed2004

Impaired microvascular function in obesity: implications for obesity-associated microangiopathy, hypertension, and insulin resistance.

BACKGROUND: Obesity is associated with an increased risk of developing microangiopathy, hypertension, and insulin resistance. We hypothesized that obesity is a primary cause of microvascular dysfunction, which may contribute to the development of these obesity-related disorders. METHODS AND RESULTS: We examined microvascular function in 16 lean (body mass index <24 kg/m2) and 12 obese (body mass index >30 kg/m2) healthy women (mean age, 38.9+/-6.7 years) in the basal state and during physiological systemic hyperinsulinemia. We determined skin capillary recruitment after arterial occlusion with capillaroscopy and skin endothelium-(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside. Obese women, compared with lean women, had higher systolic blood pressure (P<0.05), impaired insulin sensitivity (P<0.01), impaired capillary recruitment in the basal state (P<0.05) and during hyperinsulinemia (P<0.05), and impaired acetylcholine-mediated vasodilation in the basal state (P<0.05) and during hyperinsulinemia (P<0.01). Sodium nitroprusside-mediated vasodilation was similar in lean and obese women. Capillary recruitment and acetylcholine-mediated vasodilation were positively correlated with insulin sensitivity (r=0.58, P<0.01 and r=0.55, P<0.01, respectively) and negatively with blood pressure (r=-0.64, P<0.001 and r=-0.42, P<0.05, respectively) in both lean and obese women. CONCLUSIONS: Obesity is characterized by impaired microvascular function in the basal state and during hyperinsulinemia and, in both lean and obese women, microvascular dysfunction is associated with increased blood pressure and decreased insulin sensitivity. These findings are consistent with a contribution of impaired microvascular function to the development of obesity-related microangiopathy, hypertension, and insulin resistance.

Adult↗
PubMed2005

Mice with low metabolic rates are not susceptible to weight gain when fed a high-fat diet.

OBJECTIVE: Mice divergently selected for high or low food intake (FI) at constant body mass differ in their resting metabolic rates (RMRs). Low-intake individuals (ML) have significantly lower RMR (by 30%) compared with those from the high-intake line (MH). We hypothesized that MLs might, therefore, be more likely to increase their body and fat mass when exposed to a high-fat diet (HFD). RESEARCH METHODS AND PROCEDURES: We exposed both lines to a diet with 44.9% calories from fat for 3 weeks while measuring FI, fecal production, and body mass and then returned the mice to standard chow. RESULTS: When exposed to the HFD, both lines significantly decreased their FI (MH, 40% to 45%; ML, 31% to 35%). This decrease occurred simultaneously with a significant increase in apparent energy absorption efficiency (AEAE). When returned to chow, FI and AEAE returned to the levels observed prior to HFD exposure. Because of the adjustments in FI, the absorbed energy was maintained in the MLs and, thus, body mass remained constant. The MH individuals overcompensated for the elevated energy content and AEAE on the HFD and, therefore, absorbed lower energy than when feeding on chow. These mice also did not significantly change their body mass when on the HFD and must have made adjustments in their energy expenditures. Both lines and both sexes increased in fat content on the HFD, but these effects were not different between lines or sexes. DISCUSSION: We found no support for the hypothesis that mice with low RMRs were more susceptible to weight gain when fed the HFD.

Absorption↗