Insulin and blood pressure during weight loss in obese adolescents

The role of insulin in the regulation of blood pressure was evaluated in 50 obese adolescents before and after a 20-week weight loss program. When compared with 10 nonobese adolescents, the obese subjects had significantly higher systolic, diastolic, and mean arterial pressures (p = 0.005), an elevated 24-hour urinary sodium excretion (p = 0.002), an elevated fasting insulin concentration (p = 0.001), and an abnormal insulin response to an oral glucose tolerance test (sum of the insulins at 0, 1, and 2 hours post-oral glucose load; p = 0.001). We also observed a significant correlation between systolic and diastolic blood pressure (age and sex normalized) and body weight (r = 0.57, p less than 0.01 and r = 0.7, p less than 0.01), fasting insulin (r = 0.49, p less than 0.01 and r = 0.54, p less than 0.01), and sum of insulins (r = 0.42, p less than 0.01 and r = 0.46, p less than 0.01). To study the effect of weight loss on the relationship between blood pressure and insulin, the obese subjects were randomly assigned to three groups: 15 to a diet and behavior change group, 18 to a diet, behavior change, and exercise group, and 17 to an obese control group. Compared with the obese control group, the two weight loss groups each experienced a significant decrease in insulin (p less than 0.01), sum of the insulins (p less than 0.01), and blood pressure (p less than 0.01). The decrease in blood pressure during the weight loss program significantly correlated with the change in both insulin and body weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of hypothalamic dopamine in blood pressure regulation

Central dopamine is involved in the control of endocrine and autonomic nervous function. Dopamine has a central hypotensive effect which can be reproduced by the administration of dopaminergic agonists which cross the blood-brain barrier. These compounds could be useful in the treatment of hypertension as hypothalamic dopaminergic dysfunction has recently been suggested in these patients.     

An extrarenal role of aldosterone on the regulation of blood pressure

This study was designed to examine the effects of aldosterone on the distribution of extracellular fluid between the intra- and extra-vascular compartments, and to relate the changes in the fluid distribution to blood pressure in nephrectomized and nephrectomized-adrenalectomized male Wistar rats. Polyethylene catheters were inserted into the right common carotid artery and the right jugular vein, and bilateral nephrectomy with or without adrenalectomy was performed. The animals were divided into three groups: 10 nephrectomized rats (NX), 10 nephrectomized-adrenalectomized rats (NX-AX), and 10 nephrectomized-adrenalectomized and aldosterone treated rats (NX-AX-A). Aldosterone (250 micrograms/rat: Aldocorten, Ciba), mixed with sesame oil, was given subcutaneously in the NX-AX-A. After these procedures, food and water were withheld. Twenty four hours later, blood pressure and body fluid volumes were measured in the unanesthetized unrestricted condition. Mean arterial pressure (MAP) was directly recorded through the carotid catheter using electric manomater. Plasma volume (PV) and extracellular fluid volume (ECFV) were measured according to the dilution principle using 131I-RISA and 35S-Na2SO4, respectively. Interstitial fluid volume (IF) defined as ECFV minus PV and PV/IF ratio was also calculated. In NX, NX-AX and NX-AX-A, the transcapillary escape rate of albumin (TER) was determined after 6 hours. TER was obtained by measuring the disappearance of intravenously injected 131I-RISA for 2 hours after injection. The initial body weight and the changes in body weight were similar among the three groups. MAP was definitely higher in the NX than in the NX-AX and the NX-AX-A. Moreover, it was significantly higher in the NX-AX-A than in the NX-AX (p less than 0.001). Although ECFV and IF were equally and significantly reduced in the NX-AX-A and the NX-AX as compared to the NX, PV was significantly higher in the NX-AX-A than in the NX-AX (p less than 0.01), leading to a significantly lower PV/IF ratio in the latter than in the former (p less than 0.02). When a relationship between MAP and PV was examined in the rats as a whole, a significant positive correlation was found between the two parameters (r = 0.69, p less than 0.001). This relationship still held in the NX-AX and the NX-AX-A in combination (r = 0.69, p less than 0.001). TER was significantly higher in the NX-AX than in the others (p less than 0.001 vs NX, and p less than 0.02 vs NX-AX-A).(ABSTRACT TRUNCATED AT 400 WORDS)     

Role of leptin in blood pressure regulation and arterial hypertension

Leptin is a 16-kDa protein secreted by white adipose tissue that is primarily involved in the regulation of food intake and energy expenditure. Plasma leptin concentration is proportional to the amount of adipose tissue and is markedly increased in obese individuals. Recent studies suggest that leptin is involved in cardiovascular complications of obesity, including arterial hypertension. Acutely administered leptin has no effect on blood pressure, probably because it concomitantly stimulates the sympathetic nervous system and counteracting depressor mechanisms such as natriuresis and nitric oxide (NO)-dependent vasorelaxation. By contrast, chronic hyperleptinemia increases blood pressure because these acute depressor effects are impaired and/or additional sympathetic nervous system-independent pressor effects appear, such as oxidative stress, NO deficiency, enhanced renal Na reabsorption and overproduction of endothelin. Although the cause-effect relationship between leptin and high blood pressure in humans has not been demonstrated directly, many clinical studies have shown elevated plasma leptin in patients with essential hypertension and a significant positive correlation between leptin and blood pressure independent of body adiposity both in normotensive and in hypertensive individuals. In addition, leptin may contribute to end-organ damage in hypertensive individuals such as left ventricular hypertrophy, retinopathy and nephropathy, independent of regulating blood pressure. Here, current knowledge about the role of leptin in the regulation of blood pressure and in the pathogenesis of arterial hypertension is presented.     

Role of acetyl glyceryl ether phosphorylcholine in blood pressure regulation in rats

The role of an endogenously occurring acetyl glyceryl ether phosphorylcholine (AGEPC) in blood pressure regulation was studied with an AGEPC antagonist in rats with hypertension of various etiologies. The hypotensive activity of an intravenously injected AGEPC was competitively suppressed by the intravenous infusion of 3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl-2-thiazolioethylphospha te (CV-3988) and was dose-dependent. The CV-3988 was infused intravenously into one- and two-kidney, one clip hypertensive, deoxycorticosterone-salt hypertensive, adrenal regeneration hypertensive, spontaneously hypertensive, and normotensive control rats. The increase in blood pressure caused by CV-3988 infusion in spontaneously hypertensive and normotensive control rats was significant (p less than 0.01 and p less than 0.001, respectively, at 60 min) compared with that caused by vehicle infusion. The increase was not seen in rats with secondary hypertension. In rats with two-kidney, one clip hypertension, the initial rapid decrease in blood pressure seen after unclipping was significantly (p less than 0.05) inhibited by CV-3988 infusion as compared with that by vehicle infusion. These results suggest that endogenous AGEPC may participate in the blood pressure regulation and pathophysiology of some forms of hypertension in rats.     

Role of endothelium-derived nitric oxide in the regulation of blood pressure.

The role of endothelium-derived nitric oxide in the regulation of blood pressure in the anesthetized rabbit was studied with N omega-monomethyl-L-arginine (L-NMMA), a specific inhibitor of its formation from L-arginine. L-NMMA (3-100 mg.kg-1), but not its D-enantiomer, induced a dose-dependent long-lasting (15-90 min) increase in mean systemic arterial blood pressure. L-NMMA (100 mg.kg-1) also inhibited significantly the hypotensive action of acetylcholine, without affecting that of glyceryl trinitrate. Both these actions of L-NMMA were reversed by L-arginine (300 mg.kg-1), but not by D-arginine (300 mg.kg-1), indomethacin (1 mg.kg-1), prazosin (0.3 mg.kg-1), or by vagotomy. The effects of L-NMMA in vivo were associated with a significant inhibition of the release of nitric oxide from perfused aortic segments ex vivo. This inhibition was reversed by infusing L-arginine through the aortic segments. These results indicate that nitric oxide formation from L-arginine by the vascular endothelium plays a role in the regulation of blood pressure and in the hypotensive actions of acetylcholine.     

Role of adenosine in coronary blood flow regulation after reductions in perfusion pressure

We employed intracoronary infusion of adenosine deaminase to test the hypothesis that endogenous adenosine contributes to regulation of coronary blood flow following acute reductions in coronary artery pressure. In 16 closed-chest anesthetized dogs, we perfused the left circumflex coronary artery from a pressurized arterial reservoir and measured coronary blood flow following changes in perfusion pressure before and 10 minutes after the start of intracoronary adenosine deaminase, 5 U/min per kg body weight. Parallel studies showed that this dose of enzyme resulted in cardiac lymph adenosine deaminase concentrations of 3.2 +/- 0.4 U/ml. Adenosine deaminase abolished the vasodilator response to intracoronary adenosine, 4 and 8 micrograms, but had no effect on the vasodilator response to intracoronary papaverine, 200 and 300 micrograms, demonstrating enzyme efficacy and specificity. Additional experiments demonstrated that adenosine deaminase reversibly attenuated myocardial reactive hyperemia following 5- and 10-second coronary occlusions by 30% (P less than 0.05), evidence that the infused enzyme effectively degraded endogenous adenosine. However, adenosine deaminase did not alter the time course for coronary autoregulation or the steady state autoregulatory flow response over the pressure range between 125 and 75 mm Hg. Further, adenosine deaminase did not alter steady state coronary flow when perfusion pressure was reduced below the range for effective autoregulation (60-40 mm Hg). Such results show that adenosine is not essential for either coronary autoregulation or for the maintenance of coronary vasodilation when autoregulatory vasodilator reserve is expended.     

Role of angiotensin II in aldosterone regulation in the Pekin duck

The response of plasma aldosterone to increased plasma angiotensin II (AII) was evaluated in normally hydrated Pekin ducks as well as in birds in which plasma sodium had been acutely increased (+12 mmol/l) or reduced (-4 mmol/l) by the prior infusion of hypertonic saline or hypotonic glucose. In all cases, the i.v. infusion of AII at rates of 5, 15 and 45 pmol/kg per min for 1 h produced dose-dependent increases in the plasma concentration of aldosterone, with a potency that was inversely related to the sodium status. In addition, adrenal receptors for AII were demonstrated by in-vitro autoradiography and membrane-binding techniques, suggesting that the AII effect on aldosterone secretion is direct. Angiotensin II produced no change in plasma corticosterone. The infusion of KCl at 1, 2 and 5 mmol/l for 1 h increased plasma potassium by as much as 2 mmol/l, but had no influence on plasma aldosterone. Similarly, the heptapeptide angiotensin III, infused at 5, 15 and 45 pmol/kg per min for 1 h had no effect on circulating aldosterone. The results show that in ducks, AII has a physiological role in the control of aldosterone, whereas plasma potassium and angiotensin III have no such secretagogue function.     

Role of renal medullary heme oxygenase in the regulation of pressure natriuresis and arterial blood pressure

Recent studies have demonstrated that inhibition of renal medullary heme oxygenase (HO) activity and carbon monoxide (CO) significantly decreases renal medullary blood flow and sodium excretion. Given the crucial role of renal medullary blood flow in the control of pressure natriuresis, the present study was designed to determine whether renal medullary HO activity and resulting CO production participate in the regulation of pressure natriuresis and thereby the long-term control of arterial blood pressure. In anesthetized Sprague-Dawley rats, increases in renal perfusion pressure induced significant elevations of CO concentrations in the renal medulla. Renal medullary infusion of chromium mesoporphyrin (CrMP), an inhibitor of HO activity, remarkably inhibited HO activity and the renal perfusion pressure-dependent increases in CO levels in the renal medulla and significantly blunted pressure natriuresis. In conscious Sprague-Dawley rats, continuous infusion of CrMP into the renal medulla significantly increased mean arterial pressure (129+/-2.5 mm Hg in CrMP group versus 118+/-1.6 mm Hg in vehicle group) when animals were fed a normal salt diet (1% NaCl). After rats were switched to a high-salt diet (8% NaCl) for 10 days, CrMP-treated animals exhibited further increases in mean arterial pressure compared with CrMP-treated animals that were kept on normal salt diet (152+/-4.1 versus 130+/-4.2 mm Hg). These results suggest that renal medullary HO activity plays a crucial role in the control of pressure natriuresis and arterial blood pressure and that impairment of this HO/CO-mediated antihypertensive mechanism in the renal medulla may result in the development of hypertension.     

Role of the multidomain protein spinophilin in blood pressure and cardiac function regulation

Spinophilin controls intensity/duration of G protein-coupled receptor signaling and thereby influences synaptic activity. We hypothesize that spinophilin affects blood pressure through central mechanisms. We measured blood pressure and heart rate in SPL-deficient (SPL(-/-)), heterozygous SPL-deficient (SPL(+/-)), and wild-type (SPL(+/+)) mice by telemetry combined with fast Fourier transformation. We also assessed peripheral vascular reactivity and performed echocardiography. SPL(-/-) had higher mean arterial pressure than SPL(+/-) and SPL(+/+) (121+/-2, 112+/-1, and 113+/-1 mm Hg). Heart rate was inversely related to spinophilin expression (SPL(-/-) 565+/-0.4, SPL(+/-) 541+/-5, SPL(+/+) 525+/-8 bpm). The blood pressure response to prazosin, trimethapane, and the heart rate response to metoprolol were stronger in SPL(-/-) than SPL(+/+) mice, whereas heart rate response to atropine was attenuated in SPL(-/-). Mesenteric artery vasoreactivity after angiotensin II, phenylephrine, and the thromboxane mimetic (U46619) as well as change in heart rate, stroke volume, and cardiac output after dobutamine were similar in SPL(-/-) and SPL(+/+). Baroreflex sensitivity was attenuated in SPL(-/-) compared with SPL(+/-) and SPL(+/+), which was confirmed by pharmacological testing. Heart rate variability parameters were attenuated in SPL(-/-) mice. We suggest that an increase in central sympathetic outflow participates in blood pressure and heart rate increases in SPL(-/-) mice. The elevated blood pressure in SPL(-/-) mice was associated with attenuated baroreflex sensitivity and decreased parasympathetic activity. Our study is the first to show a role for the spinophilin gene in blood pressure regulation.     

Circadian variability of blood pressure in obese children

Background and aimsThe aim of the present study was to evaluate the circadian rhythm of blood pressure pattern in obese children, and to investigate if the lack of normal diurnal rhythm of blood pressure is associated with cardiovascular risk factors.Methods and results73 obese children (body weight [mean ± SD]: 89.0 ± 17.8 kg; age [mean ± SD]: 14.2 ± 2.3 years), 42 dippers and 31 non-dippers were investigated. Following ambulatory blood pressure monitoring (ABPM), physical fitness testing was performed on a treadmill. Physical working capacity at 130, -150, -170 beat/min (PWC-130, -150, -170), resting and peak oxygen consumption (VO₂rest, VO₂peak) were determined.Forty-two percent of obese children were non-dipper. PWC-130 (74.8 ± 48.8 watts; 48.0 ± 38.5 watts), PWC-150 (132.9 ± 52.1 watts; 104.2 ± 49.3 watts), PWC-170 (185.9 ± 49.5 watts; 154.9 ± 53.4 watts) and VO₂rest, ([mean ± SD]: 0.29 ± 0.08 L/min; 0.26 ± 0.07 L/min), and VO₂ peak (2.77 ± 0.61 L/min; 2.44 ± 0.62 L/min) were significantly lower in the non-dipper group, as compared to dippers (p < 0.05). The prevalence of hypertension, on the basis of ABPM, was significantly higher in the non-dipper group (45.2% vs 83.9%, p < 0.001). This is due to increased prevalence of masked hypertension in the non-dipper group (19.0% vs 32.3%, p < 0.001).ConclusionThe normal circadian variation of the blood pressure is frequently absent in obese children. Most of the non-dipper obese children are hypertensive, and their physical fitness is decreased.     

Role of bradykinin in the regulation of blood pressure and renal blood flow in DOCA-salt hypertensive rats

We examined the role of bradykinin in the onset and/or the maintenance of blood pressure and renal blood flow in deoxycorticosterone acetate (DOCA)-salt hypertensive rats by using a competitive antagonist of bradykinin [Arg-Pro-Hyp-Gly-Thi-Ser-Dphe-Thi-Arg; Hyp, L-4-hydroxyproline; Thi, beta-(2-theinyl-L-alanine)]. The intravenous injection of the bradykinin antagonist (25, 50 and 100 micrograms) produced an increase in mean arterial pressure in all rats treated with tap water, 1% NaCl and DOCA + 1% NaCl. However, the magnitude of the increase in mean arterial pressure was significantly lower in the DOCA-hypertensive rats than in the two groups of rats drinking tap water and 1% NaCl after 4 and 6 weeks, but there was no significant difference after 2 weeks. The bradykinin antagonist induced a decrease in renal blood flow in all rats. However, the extent of the fall in renal blood flow was reduced in the DOCA-hypertensive rats compared with the control rats drinking tap water. These results suggest that endogenous bradykinin is depressed in the established phase of hypertension in DOCA-hypertensive rats. It is also suggested that endogenous bradykinin may counteract the elevation of vascular resistance in the early stages of this model.     

The relationship of ambulatory blood pressure to physical activity in a tri-ethnic population of obese and nonobese adolescents

BACKGROUND: The association between physical activity (PA) and ambulatory blood pressure (ABP) is documented in adults. This association and factors that may modify it, such as obesity, have not been reported in adolescents. The aims of this study were to determine the association of PA with ABP in 11- to 16-year-old adolescents, and to examine the modifying effects of obesity and other factors. METHODS: Data on 24-h ABP and PA were obtained from 374 adolescents using the wrist actigraph. Correlations between average PA for every 5-min interval preceding each BP measurement and ABP were calculated during the awake period. Mixed-effects models were used with ABP variables as separate, dependent variables. In addition to PA scores for 5 min preceding each BP, body mass index (BMI) z-score and other variables were added to the models as covariates and as interaction terms with activity. RESULTS: Correlations of PA for 5 min preceding BP measurements were 0.22 and 0.25 for systolic blood pressure (SBP) and diastolic blood pressure (DBP) respectively. In mixed-effects analysis, each 1-unit increase in PA was associated with an increase in SBP of 0.02 mm Hg, in DBP of 0.01 mm Hg, and in HR of 0.02 beat/min (P < .0001). The association of BP with PA was significantly less for those with higher BMI z-scores (SBP, P < .001, DBP, P = .027). The associations of PA with SBP and HR were modified by sexual maturation status of the adolescents. CONCLUSIONS: This study found that PA is associated with ABP measurements. These associations are modified by obesity status and other variables. Recognizing these associations may improve the interpretation of ABP measurements.