The Journal of clinical investigation
-
We dissected and perfused outer medullary vasa recta (OMVR) from vascular bundles in the rat. Permeabilities of sodium (PNa) and urea (Pu) were simultaneously determined from the lumen-to-bath efflux of 22Na and [14C]urea. PNa and Pu were also measured by in vivo microperfusion of descending (DVR) and ascending vasa recta (AVR) at the papillary tip of Munich-Wistar rats. ⋯ Transport of [14C] urea in OMVR was reversibly inhibited by addition of unlabeled urea or phloretin to the bath and lumen, providing evidence for carrier-mediated transport. These data suggest that sodium and urea might traverse the wall of inner medullary vasa recta by a paracellular pathway while urea also crosses by a transcellular route in OMVR. Electron microscopic examination of seven in vitro perfused OMVR revealed no fenestrations and exposure of these vessels to 10 microM calcium ionophore A23187 or 1 nM angiotensin II resulted in reversible contraction, suggesting that in vitro perfused OMVR are DVR only.
-
Regional myocardial ischemia is associated with increased levels of adenosine and norepinephrine, factors that may alter activation of the beta-adrenergic receptor (beta AR)-G protein-adenylyl cyclase pathway in the heart. We have used the ameroid constrictor model to determine whether alterations in myocardial signal transduction through the beta AR-G protein-adenylyl cyclase pathway occur in the setting of chronic episodes of reversible ischemia. Pigs were instrumented with ameroid occluders placed around the left circumflex coronary artery. 5 wk later, after ameroid closure, flow and function were normal in the ischemic bed, but flow (P = 0.001) and function (P < 0.03) were abnormal when metabolic demands were increased. ⋯ In contrast, the cardiac stimulatory GTP-binding protein, Gs alpha, was increased in endocardial sections from the ischemic bed (P = < 0.05). Decreased Gi alpha 2 content was associated with decreased inhibition of adenylyl cyclase. Reduced Gi alpha 2 content, in conjunction with increased Gs alpha content in the endocardium, may provide a means by which adrenergic activation is maintained in the setting of chronic episodic myocardial ischemia.
-
Recent studies have revealed that arginine vasopressin (AVP) has at least two types of receptors in the kidney: V1a receptor and V2 receptor. In this study, microlocalization of mRNA coding for V1a and V2 receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction. Large signals for V1a receptor PCR product were detected in the glomerulus, initial cortical collecting duct, cortical collecting duct, outer medullary collecting duct, inner medullary collecting duct, and arcuate artery. ⋯ During a 72-h water restriction state, the plasma AVP level increased and V2 receptor mRNA decreased in collecting ducts. In contrast, V1a receptor mRNA did not change significantly. Thus, the two AVP receptor subtypes are distributed differently along the nephron, and these mRNAs are regulated differently in the dehydrated state.
-
The overall objective of these studies was to determine whether IgG antibody to Pseudomonas aeruginosa would modify the acute lung and pleural injury that developed over 24 h after the instillation of 10(10) live P. aeruginosa into the distal airspaces of one lung in unanesthetized sheep. Using a quantitative experimental model to measure protein permeability across the alveolar epithelial, lung endothelial, and pleural mesothelial barriers, the effect of IgG antibody to P. aeruginosa was examined under four different experimental conditions. First, the effect of IgG antibody to P. aeruginosa in the circulation was examined by instilling 10(10) live P. aeruginosa in 5% ovine albumin in sheep that had been vaccinated. ⋯ Therefore, the fourth protocol examined the prophylactic effect of instillation of the specific IgG antibody to P. aeruginosa 24 h before instillation of the bacteria. With this prophylactic regimen, epithelial, endothelial, and pleural injury were prevented, and there was a significant decrease in the number of bacteria recovered from the lung. Thus, delivery of IgG antibody to P. aeruginosa the distal airspaces of the lung alone may provide a novel therapeutic approach to preventing acute pulmonary infection caused by P. aeruginosa.
-
Lung carbonic anhydrase (CA) permits rapid pH responses when changes in regional ventilation or perfusion alter airway and alveolar PCO2. These pH changes affect airway and vascular resistances and lung compliance to optimize the balance of regional ventilation (VA) and perfusion (Q) in the lung. To test the hypothesis that these or other CA-dependent mechanisms contribute to VA/Q matching, we administered acetazolamide (25 mg/kg intravenously) to six anesthetized and paralyzed dogs and measured VA/Q relationships before and after CA inhibition by the multiple inert gas elimination technique. ⋯ Acetazolamide increased VA/Q mismatch and reduced arterial PO2 measured at equilibrium but these did not occur in the control group. There was no deterioration in VA/Q matching when systemic respiratory acidosis produced either by CO2 inhalation or 4,4'-dinitrostilbene-2,2'-disulfonate or metabolic acidosis (benzolamide or HCl) were imposed to mimic the effects of acetazolamide apart from its inhibition of lung CA. These results support the concept that lung CA subserves VA/Q matching in the normal lung.