No abstract

Urinary and renal rK1-kallikrein was studied in spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). It was demonstrated that the antiserum used for kallikrein radioimmunoassay (RIA) reacts with rK1- but not with rK7-protein. The specificity of the kininogenase assay was tested: rK7 had only 8% of the activity of rK1. Urinary kallikrein excretion by RIA was reduced by about two thirds in 5-week-old SHR compared WKY (11.5 versus 37.1µg/24h). On the contrary, the kidney content of rK1-kallikrein by RIA was increased by 40% in these rats (11.6 versus 8.4 ng/mg protein). The increase in kidney rK1 was confirmed by kininogenase assays. The same pattern of reduced urinary and increased renal rK1-kallikrein was observed in 8-week-old SHR rats. Kidney rK1-kallikrein mRNA tended to be lower (0.10 > p > 0.05) in SHR compared to WKY rats, suggesting that the increased kidney rK1 content is not due to increased rK1 synthesis. We hypothesize that the combination of high kidney content and low urinary excretion may be due to a defective mechanism for secretion of rK1 into the urine by tubular epithelial cells.

Introduced by R. H. Egdahl)Intrarenal infusion of acetylcholine, a potent vasodilator, increases sodium excretion both in normal (1, 2 ) and in edematous (3) dogs. The systemic infusion of pressor agents in addition to intrarenal vasodilators (vasoactive drugs) results in a further increment in sodium excretion ( 2, 3 ) . Micropuncture studies have demonstrated that a t least one site of action of acetylcholine is on the proximal tubule, in which both fractional and absolute sodium reabsorption decrease (4).Although vasoactive drugs decrease proximal fractional sodium reabsorption (PFSR) and increase distal delivery of filtered sodium (4), it is not clear whether this proximal effect accounts for the natriuresis. I n normal dogs, comparable increases in distal delivery can be induced by infusing hyperoncotic albumin, but sodium excretion increases only minimally ( 5 ) . In dogs with thoracic vena caval constriction (TVC dogs), saline infusion increases distal delivery without inducing natriuresis (6). From these observations, it seemed to us unlikely that depression of PFSR alone would be an adequate mechanism to explain the natriuresis induced by vasoactive drugs in normal and TVC dogs. To test the hypothesis that inhibiton of distal reabsorption is a key factor, we attempted to block the proximal effect of vasoactive drugs. In normal dogs, prior depression of PFSR by hyperoncotic albumin infusion preempted the usual proximal effects of vasoactive drugs. Nevertheless, sodium excretion increased markedly in response to these agents. These results support the view that distal inhibition is a key factor in the natriuretic response to vasoactive drugs. Inhibition both of proximal and of distal reabsorption appeared to be factors in the natriuretic response of TVC dogs to the vasoactive agents, 2llethods. Experiments were performed on 10-2 5 kg normal mongrel dogs and on chronic TVC dogs. TVC dogs were prepared as previously described from this unit (6, 7) and experiments were performed 4 to 7 days postoperatively. For this study, TVC dogs were defined as dogs with an inferior vena cava pressure greater than 15 cm saline, ascites and urinary sodium excretion of less than 200 pEq/min when challenged with a saline load equal to 10% of body weight. The experimental techniques for micropuncture were those previously described (6). The only additional procedure was that a size 26 needle, connected to a syringe by polyethylene tubing, was inserted in a retrograde direction into the main renal artery, usually at the division of the artery into its two main branches and fixed with a drop of adhesive. The needle was kept open with an infusion of 0.9% sodium chloride a t 0.5-1.0 ml/min until acetylcholine was infused into the renal artery a t 40 pg/min. I n addition, each dog was infused via a femoral vein with a vasopressor, either angiotensin or metaraminol, at initial infusion rates of 1 and 10 pg/min, respectively. The dose of either agent was adjusted as necessary during an experiment to maintain a stable elevation in blo...