SummaryAscending urinary tract infections can cause extensive damage to kidney structure and function. We have used a number of advanced techniques including multiphoton microscopy to investigate the crucial early phases of uropathogenic Escherichia coli induced pyelonephritis within a living animal. Our results reveal a previously undescribed innate vascular response to mucosal infection, allowing isolation and eradication of the pathogen. The extremely rapid host response to mucosal infection was highlighted by the triggering of a cascade of events within 3-4 h. Epithelial signalling produced an increase in cellular O 2 consumption and affected microvascular flow by clotting, causing localized ischaemia. Subsequent ischaemic damage affected pathophysiology with actin re-arrangement and epithelial sloughing leading to paracellular bacterial movement. A denuded tubular basement membrane is shown to hinder immediate dissemination of bacteria, giving the host time to isolate the infection by clotting. Suppression of clotting by heparin treatment caused fatal urosepsis. Clinically these findings may be relevant in antibiotics delivery in pyelonephritis patients and to the use of anticoagulants in sepsis.

Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting β-cells, endothelium-derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future.

We sought to determine whether tubuloglomerular feedback (TGF), activated from one nephron, affects other arterioles derived from the same cortical radial artery. Surface nephrons supplied by a single cortical radial artery were identified by injecting Ringer solution containing Fast Green from a narrow-gauge polyethylene catheter inserted via a lumbar artery into a renal artery. Stop-flow pressure was measured in an identified nephron from such a grouping. In one series, increasing end-proximal flow rate from 0 to 50 nl/min of synthetic tubular fluid in one member of an identified pair of nephrons reduced stop-flow pressure by 1.3 +/- 0.2 mmHg in the other member. When the nephrons were derived from different cortical radial arteries, the stop-flow pressure changed -0.2 +/- 0.1 mmHg. In another series, increasing flow in the adjacent nephron from 0 to 50 nl/min decreased stop-flow pressure 3.9 +/- 0.9 mmHg, and increasing flow in the adjacent nephron by the same amount when flow in the first nephron was 50 nl/min decreased stop-flow pressure 3.4 +/- 0.7 mmHg. These results indicate the operation of an interaction among nephrons derived from a common cortical radial artery. Such an interaction could produce a cooperative effect larger than that predicted from measured single-nephron responses when systemic arterial pressure changes.

The effects of 1-2 h of hypothermia at 28 degrees C and rewarming on renal function were investigated in anaesthetized rats, using conventional clearance methods and the micropuncture technique. Renal blood flow (RBF) decreased from 7.3 +/- 0.51 mL min-1 at 37.5 degrees C (control) to 4.0 +/- 0.47 at 28 degrees C, with almost complete restoration to 6.9 +/- 0.59 mL min-1 after rewarming. Systemic blood pressure remained essentially unaltered. The RBF reduction seen during hypothermia was due to a 75% increase in vascular resistance, mainly attributable to constriction of the afferent arteriole and increased blood viscosity. This was accompanied by a decline in glomerular capillary pressure from 56.7 +/- 0.6 to 46.4 +/- 1.3 mmHg, overshooting to 59.0 +/- 0.7 mmHg. The glomerular filtration rate (GFR) decreased from 1.1 +/- 0.08 to 0.6 +/- 0.04 mL min-1, returning to 1.0 +/- 0.07 after rewarming, a pattern also observed for single nephron GFR. This resulted from a decrease in net driving force for glomerular filtration, whereas the filtration coefficient was not affected. Both proximal and distal tubular fluid flow decreased, but fractional reabsorption remained unchanged. In contrast, urine flow increased from 1.8 +/- 0.16 to 5.7 +/- 1.08 microL min-1, returning to 2.1 +/- 0.18, the increase during hypothermia mainly resulting from a disproportionately reduced fluid reabsorption beyond the mid-distal tubule.

This study investigated the mechanisms for glucose-induced islet blood flow increase in rats. The effects of adenosine, adenosine receptor antagonists, and vagotomy on islet blood flow were evaluated with a microsphere technique. Vagotomy prevented the islet blood flow increase expected 3, 10, and 20 min after injection of glucose, whereas theophylline (a nonspecific adenosine receptor antagonist) prevented the islet blood flow increase from occurring 10 and 20 min after glucose administration. Administration of selective adenosine receptor antagonists suggested that the response to theophylline was mediated by A1receptors. Exogenous administration of adenosine did not affect islet blood flow, but local accumulation of adenosine, induced by the adenosine uptake inhibitor dipyridamole, caused a doubling of islet blood flow. In conclusion, the increased islet blood flow seen 3 min after induction of hyperglycemia is caused by the vagal nerve, whereas the increase in islet blood perfusion seen at 10 and 20 min after glucose administration is caused by both the vagal nerve and adenosine.