Acute renal failure was induced in heparinized rats by clamping the renal artery for 45 min. Ten minutes after recirculation the intrarenal blood flow distribution was measured. For this purpose labelled microspheres were injected together with 86-Rb chloride. The microspheres were used for determination of cardiac output, total renal and cortical blood flow, and 86-Rb for calculations of medullary blood flow. Total renal blood flow was reduced from 7.6 to 3.8 ml . min-1 . g-1 and cortical blood flow was reduced from 11.7 to 7.0 ml . min-1 . g-1. In the outer stripe of the medulla there was a reduction from 2.5 to 1.4 ml . min-1 . g-1. In the inner stripe there was a more pronounced reduction from 1.8 to 0.2 ml . min-1 . g-1 and in the inner zone from 0.8 to 0.1 ml . min-1 . g-1. The marked reduction in the blood flow to the renal medulla after recirculation is suggestive for a medullary ischemia, which might be responsible for the characteristic dysfunctions in acute renal failure.

The influence of neutrophils on peritubular capillary permeability and intravascular red blood cell (RBC) aggregation after renal ischemia was studied in anesthetized Sprague-Dawley rats. Intraperitoneal administration of antineutrophil serum (ANS) reduced the number of neutrophils in the blood to 3% of normal. The control group received an equal volume of inactive serum. Renal macromolecular capillary permeability was studied from 1) extravasation of albumin and 2) plasma to lymph transport of plasma proteins and of neutral and negatively charged lactate dehydrogenase (LDH). The net driving force (NDF) for fluid transfer over the peritubular capillary membrane was determined by the micropuncture technique. The intrarenal distributions of neutrophils and RBC were measured by a histochemical method and 51Cr-labeled RBC, respectively. Under preischemic control conditions neither macromolecular permeability nor renal clearance of inulin was affected by ANS. However, the steep increase in the macromolecular transport from plasma to lymph resulting from 45 min of ischemia and reperfusion was blunted by ANS, and preischemic control values were restored after 1 h of recirculation. In the control group the mass transport of plasma proteins increased twofold and that of both neutral and negatively charged LDH fourfold. NDF was equal in the two groups. In the ANS-treated animals the intrarenal neutrophil content was only 2% of the control. Neutrophils were found mainly in the cortex, whereas RBC aggregation was observed only in the renal medulla. It is concluded that neutrophils mediate postischemic capillary leakage. It is suggested that this leakage underlies RBC aggregation and incomplete return of blood flow in the renal medulla after ischemia.

In the classical Starling model the hydrostatic pressure in the pores is generally lower than that in capillary plasma, a phenomenon that necessitates the assumption of a rigid porous membrane. In flexible gel membranes, the capillary pressure is suggested to be balanced by a gel swelling pressure generated by negative fixed charges. Regarding the fluid transfer, the transmembranous electrical potential gradient will generate a net driving electroosmotic force. This force will be numerically similar to the net driving Starling force in small pores, but distinctly different in large pores. From previous data on the hydrostatic and colloid osmotic forces, the fixed charge density at the two interfaces of 1) the glomerular and 2) the peritubular capillary membrane were calculated and used to predict the flux of a series of charged protein probes. The close fit to the experimental data in both the capillary beds is in line with the gel concept presented. The gel concept (but hardly a rigid membrane) explains the ability of capillary membranes to alter their permeability in response to external forces. Gel membranes can furthermore be predicted to have a self-rinsing ability, as entrapped proteins will increase the local fixed charge density, leading to fluid entry into the region between the particle and the pore rim, which by consequent widening of the channel will facilitate extrusion of trapped proteins.

The effect of (1) renal denervation and (2) stimulation of the renal nerve on the regional renal blood flow were determined by the Rb uptake method. Under control conditions the total renal blood flow was 3.64 +/- 0.09 ml X min-1 X g-1 tissue increasing significantly (p less than 0.02) to 4.39 +/- 0.28 ml X min-1 X g-1 after denervation. Upon stimulation of the peripheral portions of the sectioned renal nerves the blood flow decreased almost linearly with the frequency of stimulation reaching 0.99 +/- 0.24 ml X min-1 X g-1 at 10 Hz. Utilizing the relation between blood flow and stimulation frequency the control blood flow correspond to a spontaneous activity of 1.5 Hz. As expected the cortical blood flow responded in the same way as for the total renal blood flow. In the renal medulla denervation gave a much more pronounced response where e.g. the inner medullary flow increased from 0.88 +/- 0.09 to 1.30 +/- 0.16 ml X min-1 X g-1, i.e. a 50% increase (p less than 0.05). Stimulation with 2 Hz produced a steep fall in the blood flow, whereafter it decreased linearly with the stimulation frequency reaching 0.11 ml X min-1 X g-1 at 10 Hz stimulation. This demonstrates again that the renal medulla is sensitive to renal nerve activity primarily in the low level range. It should be remarked, however, that the 86-Rb uptake method reflects the effective blood flow, which might differ from the blood flow in absolute terms.(ABSTRACT TRUNCATED AT 250 WORDS)

5-HT is involved in micturition control. In the rat, stimulation of the 5-HT(1A) receptor excites, whereas 5-HT(1A) receptor antagonism inhibits micturition. The present study examined the effects of a new, highly selective, 5-HT(1A) receptor antagonist, NAD-299, on micturition in rats. Comparisons were made with WAY100635, a well-characterised antagonist at the 5-HT(1A) receptor. Female Sprague-Dawley rats, conscious or anaesthetised, were used for cystometric studies. Intravenous (i.v.), intraarterial (i.a.), intrathecal (i.t.) or intracerebroventricular (i.c.v.) catheters were implanted for drug administration. In vitro, rat bladder strips were contracted by carbachol or electrical stimulation of nerves. The effects of NAD-299, WAY100635 and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT(1A) receptor agonist) on cystometric parameters and contraction of bladder strips were recorded. In conscious rats, i.v. NAD-299 and WAY100635 at 1 micro mol kg(-1) increased bladder capacity (24+/-13% and 27+/-19% respectively) and decreased micturition pressure (16+/-8% and 12+/-10% respectively). Given i.a., 5-HT 0.25 micro mol kg(-1) and 8-OH-DPAT 0.37 micro mol kg(-1) stimulated micturition. The effect of 8-OH-DPAT, but not those of 5-HT, was blocked by i.a. NAD-299. 8-OH-DPAT 0.03 micro mol given i.t. or i.c.v. stimulated micturition, an effect blocked by WAY100635 0.1 micro mol, given i.t or i.c.v. NAD-299 or WAY100635 (0.1 micro mol i.t.) were without significant effects, but given i.c.v. at 0.1 micro mol both drugs increased bladder capacity (34+/-12% and 22+/-13% respectively). Neither NAD-299 nor WAY100635 up to 10(-5) M had effects on electrically- or carbachol-induced contractions of rat bladder strips. NAD-299 1 micro mol kg(-1) i.v. suppressed oxyhaemoglobin-induced detrusor over-activity. It is concluded that NAD-299, acting at a supraspinal site, can inhibit micturition in the rat.