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The effects of varying degrees of acute systemic nitric oxide (NO) synthesis inhibition on renal and systemic hemodynamic, natriuretic and neurohumoral responses were investigated. Three different intravenous infusions of N(super G)-nitro-L-arginine methyl ester were studied for arterial pressure, renal blood flow, systemic vascular resistance, fractional sodium and lithium excretion, glomerular filtration rate and renal vascular resistance in healthy men. It was found that renal circulation is not more sensitive to the effects of NO synthesis inhibition than systemic circulation.

Lameris, T. W., A. H. van den Meiracker, F. Boomsma, G. Alberts, S. de Zeeuw, D. J. Duncker, P. D. Verdouw, and A. J. Man in 't Veld. Catecholamine handling in the porcine heart: a microdialysis approach. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1562-H1569, 1999.--Experimental findings suggest a pronounced concentration gradient of norepinephrine (NE) between the intravascular and interstitial compartments of the heart, compatible with an active neuronal reuptake (U1) and/or an endothelial barrier. Using the microdialysis technique in eight anesthetized pigs, we investigated this NE gradient, both under baseline conditions and during increments in either systemic or myocardial interstitial fluid (MIF) NE concentration. At steady state, baseline MIF NE (0.9 [+ or -] 0.1 nmol/l) was higher than arterial NE (0.3 [+ or -] 0.1 nmol/l) but was not different from coronary venous NE (1.5 [+ or -] 0.3 nmol/l). Local U1 inhibition raised MIF NE concentration to 6.5 [+ or -] 0.9 nmol/l. During intravenous NE infusions (0.6 and 1.8 nmol [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1], the fractional removal of NE by the myocardium was 79 [+ or -] 4% to 69 [+ or -] 3%, depending on the infusion rate. Despite this extensive removal, the quotient of changes in MIF and arterial concentration ([Delta]MIF/[Delta]A ratio) for NE were only 0.10 [+ or -] 0.02 for the lower infusion rate and 0.11 [+ or -] 0.01 for the higher infusion rate, whereas U1 blockade caused the [Delta]MIF/[Delta]A ratio to rise to 0.21 [+ or -] 0.03 and 0.36 [+ or -] 0.05, respectively. From the differences in [Delta]MIF/[Delta]A ratios with and without U1 inhibition, we calculated that 67 [+ or -] 5% of MIF NE is removed by UI. Intracoronary infusion of tyramine (154 nmol [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1]) caused a 15-fold increase in MIF NE concentration. This pronounced increase was paralleled by a comparable increase of NE in the coronary vein. We conclude that U1 and extraneuronal uptake, and not an endothelial barrier, are the principal mechanisms underlying the concentration gradient of NE between the interstitial and intravascular compartments in the porcine heart. norepinephrine; spillover; pig; myocardial interstitium

Cardiovascular and catecholaminergic activity during mental load were studied in patients with Tourette syndrome. Patients and controls performed the Color Word Test, preceded by a baseline period, with continuous measurements of heart rate and blood pressure. Blood samples for assay of plasma catecholamine concentrations were obtained before and during the test. The patients showed higher heart rate and blood pressure during baseline than controls, but no differences regarding plasma catecholamines. The tics corresponded with transient increases in heart rate and blood pressure. Spectral analysis of cardiovascular variability during mental load gave only limited evidence of increased sympathetic activity and no alterations in parasympathetic activity in the patients. Therefore, our findings indicate enhanced cardiovascular activity in the patients but not during mental load. The effects of tics on the cardiovascular parameters illustrate the functional complexity of the autonomic nervous system in Tourette syndrome.

Objective: Heart failure is common in individuals with type 2 diabetes, and early detection of individuals at risk may offer opportunities for prevention. We aimed to explore 1) prospective associations of B-type natriuretic peptide (BNP) levels in a non-heart failure range with changes in markers of left ventricular (LV) function and 2) possible effect modification by type 2 diabetes in a population-based cohort.Research Design and Methods: Echocardiographic measurements were performed at baseline (2000-2001) and follow-up (2007-2009), together with standardized physical examinations and BNP measurements on 300 individuals (mean age 66 years, 32% with type 2 diabetes) of the longitudinal Hoorn Study. Multivariate linear regression analyses were performed to investigate associations of baseline BNP (<100 pg/mL) in individuals without prevalent heart failure at baseline with changes in LV mass index, LV ejection fraction, left atrial volume index, and ratio of early diastolic LV inflow velocity (E) to early diastolic lengthening velocity (e') (E/e').Results: In all individuals, higher BNP was associated with 8-year increases in left atrial volume index. Higher BNP was also associated with increasing LV mass index and E/e'. These associations were significantly stronger in individuals with type 2 diabetes compared with the nonsignificant associations in individuals without type 2 diabetes.Conclusions: This 8-year follow-up study shows that higher BNP levels in a non-heart failure range were associated with an increased LV mass and deteriorated LV diastolic function, particularly in individuals with type 2 diabetes. This implies that the presence or absence of type 2 diabetes should be taken into account if BNP levels are used to assess future heart failure risk. [ABSTRACT FROM AUTHOR]

Brain-derived natriuretic peptide (BNP) is a cardioprotective peptide released, together with the inactive NH2-terminal part of its prohormone (NT-pro-BNP), in response to different kinds of myocardial stress. Hypoglycemia and hypoxemia are conditions that threaten cellular function and hence potentially stimulate BNP release. BNP interacts with the renin-angiotensin system (RAS). The aim of this study was, therefore, to explore if basal RAS activity has an impact on NT-pro-BNP concentrations during myocardial stress induced by hypoglycemia and hypoxemia. From a cohort of 303 healthy young men, 10 subjects with high-RAS activity and 10 subjects with low-RAS activity (age 26 ± 1 yr; mean ± SE) were studied in a single-blinded, randomized, counterbalanced, crossover study on three occasions separated by at least 3 wk: 1) hypoglycemia (mean nadir plasma glucose 2.7 ± 0.5 mmolIl), 2) hypoxemia (mean nadir Po2 5.8 ± 0.5 kPa), and 3) normoglycemic normoxia (control). NT-pro-BNP was measured at baseline, during the stimuli, and in the recovery phase. Hypoxemia was associated with a 9% increase in NT-pro-BNP from 2.2 ± 1.5 pmolIl at baseline to 2.4 ± 1.5 pmolIl during hypoxemia (P < 0.001). Hypoglycemia did not affect the NT-pro-BNP level. RAS activity had no impact on NT-pro-BNP levels during hypoglycemia and hypoxemia. Hypoxemia, but not hypoglycemia, stimulates NT-pro-BNP. This indicates that cardiac defense mechanisms against hypoglycemia, if any, are probably different from those against hypoxemia. Basal RAS activity had no impact on NT-pro-BNP levels. [ABSTRACT FROM AUTHOR]

Aims: Activity in the renin-angiotensin system (RAS) may influence the susceptibility to cardiac arrhythmia. To study the effect of basal RAS activity on cardiac repolarization during myocardial stress induced by hypoglycaemia or hypoxaemia in healthy humans. Methods and Results: Ten subjects with high RAS activity and 10 subjects with low RAS activity were studied on three different occasions: (i) hypoglycaemia (nadir P-glucose 2.7 +/- 0.5 mmol/L), (ii) hypoxaemia (nadir pO(2) 5.8 +/- 0.5 kPa), and (iii) normoglycaemic normoxia (control day). QT parameters were registered by Holter monitoring. Hypoglycaemia and hypoxaemia induced QTc prolongation (P < 0.001, both stimuli). The QT/RR slope and the VR increased as a function of hypoglycaemia, but were unaffected by hypoxaemia. Low RAS activity was associated with a steeper QT/RR slope in the recovery phase after both stimuli: hypoglycaemia: P = 0.04; hypoxia: P = 0.03. RAS activity had no impact on QTc [P = 0.48 (hypoglycaemia) and P = 0.40 (hypoxaemia)] or any of the other outcome variables. Conclusion: Basal RAS activity has significant impact on QT dynamics, but not the corrected QT interval, during recovery from hypoglycaemia and hypoxaemia. The impact, however, is modest and more subtle than initially expected. The clinical relevance is unclear. [ABSTRACT FROM AUTHOR]

Objective.-To compare the contractile responses to alpha-adrenergic receptor agonists and 5-HT in the rat carotid artery after ovariectomy and subsequent hormone replacement with 17beta-estradiol, progesterone, or the combination of 17beta-estradiol and progesterone. Background.-The prevalence of migraine is higher in women than in men, and changes in 17beta-estradiol levels seem to affect the frequency of attacks in female migraineurs. However, the underlying mechanisms are not yet completely understood. Methods.-After 1 week of acclimatization (Day 0), female Sprague-Dawley rats were either sham-operated or bilateral ovariectomized. One week later (Day 7), the ovariectomized rats were subcutaneously implanted with a pellet releasing over a 21-day period either placebo, 0.25 mg 17beta-estradiol, 50 mg progesterone, or the combination of the 2 hormones. Blood samples were collected on Days 0, 7, and 21 to measure plasma norepinephrine and epinephrine. On days 25 to 28, the animals were killed to isolate carotid artery and mount its segments in Mulvany myographs. Cumulative concentration response curves to alpha-adrenergic receptor agonists and 5-HT were constructed in the absence or presence of suitable antagonists. Results.-The potency of norepinephrine in ovariectomized rats was significantly reduced in animals treated with progesterone as compared to those with placebo. In placebo-treated ovariectomized animals there was a noticeable response mediated by alpha(2)-adrenoceptors, in contrast to that in sham-operated or ovariectomized rats treated with 17beta-estradiol and progesterone, either alone or in combination. The plasma levels of norepinephrine and epinephrine were not significantly affected by either ovariectomy or the subsequent hormone replacement. The potency of 5-HT was significantly reduced in animals having circulating sex hormones as compared to that in placebo-treated ovariectomized animals. Conclusion.-Taken together, our results indicate that circulating progesterone and/or 17beta-estradiol may reduce the contraction of the rat carotid artery in response to norepinephrine and 5-HT. This effect of female sex hormones might be one of the factors through which these hormones aggravate migraine in women. [ABSTRACT FROM AUTHOR]