To evaluate the effect of hyper- and hypotonicity on proximal convoluted tubule (PCT) cell volume, nonperfused PCT were studied in vitro with hypertonic solutions containing sodium chloride, urea, or mannitol (450 mosmol/kg H2O) and with hypotonic low sodium chloride solutions (160 mosmol/kg H2O). When the tubules were subjected to hypertonic peritubular solutions containing NaCl, cell volume immediately decreased by 15.5% and remained constant throughout the experimental period (60 min). With mannitol, the initial decrease was identical to that with NaCl (17.7%), but the PCT volume increased slightly during the experimental period. With urea, the decrease in cell volume was smaller (7%) and transient. In hypotonicity, the PCT swelled rapidly, but this swelling was followed by a rapid regulatory phase in which PCT volume nearly returned to control values after less than 10 min. With a potassium-free peritubular medium or 10(-3) M ouabain, the regulatory phase of hypotonicity completely disappeared, whereas the cells did not maintain their reduced volume in NaCl-induced hypertonicity. These results suggest that Na-K-ATPase plays an important role in the maintenance of a reduced cellular volume in hypertonicity and in the regulatory phase of hypotonicity, probably by an active extrusion of sodium and water from the cell.

No abstract

The present studies examined the role of the renin-angiotensin system as a modifier of the renal vasomotor response to bradykinin. Renal arterial bradykinin infusion (80 ng.kg-1.min-1) initially resulted in increased renal blood flow (RBF). The secretory rates of renin and prostaglandins increased after 60 min. With continued bradykinin administration (120 min) RBF and prostaglandin secretory rates returned toward control values, although renin secretory rate remained elevated (P less than 0.02). After prostaglandin synthetase inhibition, RBF decreased and bradykinin administration returned RBF to control values. Prostaglandin secretory rates decreased after meclofenamate (P less than 0.005). Continued bradykinin infusion resulted in a return of the renin secretory rate to control values. The administration of bradykinin after competitive inhibition of angiotensin II resulted in a sustained increase in renal blood flow. These results suggest that the initial bradykinin-induced renal hyperemia is only partially dependent on enhanced prostaglandin release, the increase in renin secretion by bradykinin infusion after prostaglandin synthetase inhibition is consistent with a bradykinin and renin interaction, and the lack of a sustained hyperemia after bradykinin is related to increased renin-angiotensin system activity.

The influence of thiopental anesthesia on renal tubular sodium reabsorption was investigated in the well-trained dog. After administration of the anesthetic, renal sodium reabsorption was depressed, leading to the enhanced excretion of sodium and water. Associated with this response was a decrease in the plasma levels of epinephrine and norepinephrine. Neither renal hemodynamic functions nor the humoral factors, prostaglandin E, plasma renin activity, or arginine vasopressin appeared to be the major determinants of the natriuresis. These observations suggest that the administration of thiopental depresses renal sympathetic nerve activity, thereby diminishing the renal tubular transport of sodium.

The mechanisms responsible for renal autoregulation continue to arouse considerable interest, and much of the present controversy is centered upon the role of the renin-angiotensin system in modulating the renal hemodynamic response to alterations in renal arterial pressure. Britton proposed a renin-renal autoregulation hypothesis which postulated that plasma angiotensinogen (renin substrate) and converting enzyme interact with cytoplasmic renin at the luminal surfact of the wall of the afferent arteriole to affect the arterial tone (1). In an earlier study, Waugh and Shanks observed that perfusion of isolated kidneys with an artificial colloidal perfusate resulted in loss of autoregulation, while the addition of fresh plasma to the perfusate restored the autoregulatory phenomenon (2). If the renin-angiotensin system is responsible for renal autoregulation and the presence of angiotensin converting enzyme is an essential participant in the autoregulatory process, then the infusion of an angiotensin converting enzyme inhibitor into the renal circulation should modify renal autoregulation. The current study was designed to evaluate the effects on renal autoregulation of limiting the conversion of angiotensin I to angiotensin I1 during a reduction in renal perfusion pressure.Methods. Experiments were performed on 15 female dogs (wt: 19.2 * 1.2 kg) anesthetized with intravenous pentobarbitol (30 mg/ kg) and placed on a positive pressure respirator .l During surgical preparation an infu-sion of Ringers solution was started and approximately 400 ml administered over 2 hr to replace fluid losses. Catheters were introduced into both ureters via a suprapubic incision and a femoral artery was cannulated to withdraw blood samples as well as to monitor blood pressure. The left kidney was exposed through a retroperitoneal flank incision and with a minimum of dissection the aorta, left renal artery and ovarian vein were exposed. A modified Blalock clamp (3) was applied loosely across the aorta cephalad to the right renal artery. The ovarian vein was cannulated with a length of Teflon tubing and the tip advanced to the orifice of the renal vein. The curved shaft of a #25 gauge needle, attached to two lengths of tubing by a ''Y" connection, was inserted into the left renal artery for infusion of 0.9% saline solution, angiotensin I, and angiotensin converting enzyme inhibitor (SQ20881)2 at a rate of 0.5 ml/min. A minimum of 2 hr was allowed to elapse for recovery following the surgical procedures. During this interval appropriate priming and maintenance infusions of p-aminohippurate (PAH) and 1251-iothalamate (Abbott Laboratories, No. Chicago, Ill.) were administered and 30-45 min were allowed for equilibration of these substances before urine collection periods of 20 min duration were started. Blood samples from the femoral artery and renal vein were withdrawn 3 min before the mid point of each period.To determine the effectiveness of the intra-~ ~ ~ ~~