The American journal of physiology
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The maintenance of constant cerebral blood flow (CBF) as arterial blood pressure is reduced, commonly referred to as CBF-pressure autoregulation, is typically characterized by a plateau until the vasodilatory capacity is exhausted at the lower limit, after which flow falls linearly with pressure. We investigated the effect of cortical, as opposed to systemic, nitric oxide synthase (NOS) inhibition on the lower limit of CBF-pressure autoregulation. Forty-four Sprague-Dawley rats were anesthetized with halothane and N2O in O2. ⋯ No changes in lower limit for the other agents or conditions, including 105 or 35 min of aCSF or 35 min of L-NNA suffusion, were detected. The lack of effect on the lower limit with D-NNA suffusion suggests an enzymatic mechanism, and the lengthy L-NNA exposure of 105 min, but not 35 min, suggests inhibition of a diffusionally distant NOS source that mediates autoregulation. Thus cortical suffusion of L-NNA raises the lower limit of autoregulation, strongly suggesting that nitric oxide is at least one of the vasodilators active during hypotension as arterial pressure is reduced from normal.
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Circulating leptin concentrations are raised in animal models of inflammation and sepsis. The purpose of this study was to determine the effect of sepsis on serum leptin concentration in humans and to examine the relationship between leptin and the metabolic consequences of sepsis. Resting energy expenditure, insulin sensitivity, and fasting serum leptin, plasma insulin, and cortisol concentrations were measured in 20 subjects with intra-abdominal sepsis and 20 healthy control subjects, before and during a 2-h period of euglycemic hyperinsulinemia. ⋯ Multiple regression analyses additionally indicated that percent body fat, fasting plasma insulin, and plasma cortisol, but not sepsis, were significant and independent determinants of serum leptin concentration. No relationship between leptin and resting energy expenditure or insulin sensitivity was identifiable. A major metabolic role for leptin in human sepsis therefore appears unlikely.
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In the renal inner medullary collecting duct (IMCD), vasopressin regulates two key transporters, namely aquaporin-2 (AQP2) and the vasopressin-regulated urea transporter (VRUT). Both are present in intracellular vesicles as well as the apical plasma membrane. Short-term regulation of AQP2 has been demonstrated to occur by vasopressin-induced trafficking of AQP2-containing vesicles to the apical plasma membrane. ⋯ In addition, differential centrifugation of inner medullary homogenates from Brattleboro rats treated with DDAVP for 60 min revealed a marked depletion of AQP2 from the low-density membrane fraction (enriched in intracellular vesicles) but did not alter the quantity of VRUT in this fraction. Finally, AQP2-containing vesicles immunoisolated from a low-density membrane fraction from renal inner medulla did not contain immunoreactive VRUT. Thus vasopressin-mediated regulation of AQP2, but not of VRUT, depends on regulated vesicular trafficking to the plasma membrane.
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Fos immunoreactivity was used to map the neuronal population groups activated after sodium ingestion induced by peritoneal dialysis (PD) in rats. Oxytocin immunoreactivity in combination with Fos immunoreactivity was also analyzed to evaluate whether the oxytocinergic neurons of the paraventricular nucleus of the hypothalamus (PVN) are activated during the satiety process of sodium appetite. Sodium ingestion stimulated by PD produced Fos immunoreactivity within defined cells groups of the lamina terminalis and hindbrain areas such us the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. ⋯ Approximately 27 and 2.1%, respectively, of the activated dorsomedial cap and parvocellular posterior subnuclei of the PVN, which project to the hindbrain, were oxytocinergic. Our data indicate that specific neuronal groups are activated during the satiety process of sodium appetite, suggesting they may form a circuit subserving sodium balance regulation. They also support a functional role for the oxytocinergic neurons in this circuit.
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Phospholipid vesicles encapsulating purified hemoglobin (HbV) were developed to provide O2-carrying capacity to plasma expanders. Microvascular perfusion was determined for HbV with different O2 affinity (P50 = 9, 16, and 30 mmHg) prepared by coencapsulating pyridoxal 5'-phosphate (PLP) at the molar ratios of [PLP]/[Hb] = 0, 0.5, and 3, respectively (cf. hamster blood, P50: 28 mmHg), and suspended in 8 g/dl human serum albumin (HSA). Eighty percent of the red blood cell (RBC) mass of conscious Syrian golden hamsters fitted with dorsal skinfold windows was substituted with either of the HbV-HSA suspensions, washed hamster RBC suspended in HSA (RBC-HSA), and HSA alone. ⋯ Microvascular perfusion and microvascular and interstitial O2 tensions in the HbV (P50 = 16 and 30)-HSA groups were significantly higher than those in the HSA group. The O2 release rate from the HbV was 18-32 s-1 vs. 4.4 s-1 for RBC. Functional capillary density was improved from 17 to 41% on average by decreasing P50 from 30 to 16 mmHg, which appears to be an optimal value for the P50 in this system.