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Effect of KCl infusion on renin secretory rates and aldosterone excretion in dogs.

The effects of unilateral intrarenal arterial KCl infusion in dogs (12 mueq/kg per min) on bilateral renal function, renin secretory rates, and aldosterone excretion were studied. During KCl infusion, infused-side renal arterial plasma [K+] increased by 2.2 +/- 0.6 meq/liter. Systemic plasma [K+] simultaneously rose by 0.6 +/- 0.1 meq/liter. Plasma renin activity decreased 29 +/- 9%, and the decrease correlated with the increases in plasma [K+]. Renin secretory rate decreased bilaterally, the decrease being greater in each experiment on the infused side. Aldosterone excretion increased during KCl infusion by 72 +/- 17%, despite a decrease in plasma renin activity. With KCl infusion there was a bilateral increase in K+ excretion, and a positive correlation was observed between the net alterations in K+ and Na+ excretion. No significant alterations in systemic blood pressure, glomerular filtration rate, total renal blood flow, or intracortical renal blood flow distribution were observed. These studies suggest that K+ inhibits the release of renin by an intrarenal mechanism, which may be related to a K+-induced alteration in Na+ absorption.

Aldosterone

Maximal proton secretory rate of rat distal tubules is higher during chronic metabolic alkalosis.

In vivo microperfusion studies show augmented proton secretion in the distal tubule of rats with chronic metabolic alkalosis. The present studies used the same technique to determine whether this augmented proton secretion is due predominantly to an increase in substrate affinity or alternatively to a predominant increase in the maximal proton secretory rate. Surface distal tubules of alkalotic and control rats were microperfused in vivo with solutions containing increasing concentrations of HCO3. Proton secretion was determined as the difference between measured net HCO3 reabsorption and passive HCO3 transport calculated by use of the permeability derived from perfusing with a HCO3-free solution. Proton secretion was expressed as a function of the initial luminal HCO3 concentration and was assumed to follow saturable Michaelis-Menten kinetics. Alkalotic animals had a significantly higher Km (33.9 vs. 21.6 mM, P less than 0.03) and Vmax (223.8 vs. 99.1 pmol.mm-1.min-1, P less than 0.001) compared with control. These data are consistent with the augmented proton secretion in the distal tubule of alkalotic animals as predominantly due to an increased maximal proton secretory rate rather than to increased substrate affinity.

Alkalosis

Hepatic clearance and biliary secretory rate maximum of taurocholate in the recirculating and single pass isolated perfused rat liver. Effects of the cholestatic agent, estradiol-17 beta-(beta-D-glucuronide).

The ability of the cholestatic steroid glucuronide, estradiol-17 beta-(beta-D-glucuronide) (E(2)17G), to inhibit the hepatic clearance (ClH) and biliary secretory rate maximum (SRm) of taurocholate was investigated in the recirculating and single pass isolated perfused male rat liver. In the recirculating perfused liver, E(2)17G (0, 2, 4, or 6 mumol) was added as a bolus dose to the reservoir at zero time while taurocholate was infused into the portal vein in increasing amounts (15, 30, 45, or 60 mumol/mL; 1 mL/hr for 15 min each). E(2)17G (4 mumol) caused a significant (P less than 0.05) inhibition of bile flow and bile acid secretion at 10-15 min during infusion of 15 mumol/hr taurocholate but did not inhibit the SRm which occurred at 42 min, indicating that E(2)17G had not caused an irreversible inhibition of taurocholate transport. E(2)17G (6 mumol) caused a profound and irreversible inhibition of bile flow attributable to retention of E(2)17G in the liver. The noncholestatic estradiol-3-(beta-D-glucuronide) (E(2)3G; 6 mumol) had no significant effect on bile flow or the SRm. In the single pass perfused liver (10 mL/min flow rate), E(2)17G (0, 1, 2, 5, or 10 nmol/mL) or E(2)3G (2 nmol/mL) was added to the perfusate resulting in a stable infusion to the liver. [3H]Taurocholate was infused into the portal vein in increasing amounts to give inflow concentrations (Cin) of 25, 50, 75 or 100 nmol/mL. In the absence of E(2)17G, taurocholate ClH decreased from 0.92 to 0.70 mL/min/g liver with increasing taurocholate concentrations. Neither E(2)17G nor E(2)3G altered the ClH of 25 nmol/mL taurocholate. E(2)17G (10 nmol/mL) inhibited bile flow and bile acid secretion first at 20-25 min, followed by inhibition of ClH of 75 and 100 nmol/mL taurocholate (35-60 min). In contrast, E(2)3G stimulated bile acid secretion and increased the SRm by 80%. Thus, at doses that did not block its own elimination, E(2)17G did not cause an irreversible inhibition of taurocholate transport into bile. E(2)17G did not directly inhibit the uptake of taurocholate into the liver but first inhibited the biliary excretion of taurocholate, resulting in its intrahepatic accumulation and decreased clearance from the perfusate.

Animals

Elevated growth hormone secretory rate in premature infants: deconvolution analysis of pulsatile growth hormone secretion in the neonate.

Premature infants have higher circulating concentrations of growth hormone (GH) than term infants. Previous investigations of these differences have used sampling frequencies of every 30 min with subsequent application of pulse detection algorithms, such as the CLUSTER program, to assess serum GH pulse parameters. To determine differences in GH secretory rates or GH t1/2 values between premature and term infants, we have sampled 11 neonates at 15-min intervals. We performed deconvolution analysis of the resultant plasma GH values to estimate GH secretory and clearance parameters. Five premature infants (gestational age range 24-34 wk) and six term infants (gestational age range 38-42 wk) were sampled every 15 min for 6 h. All subjects had indwelling arterial catheters. GH was measured (in duplicate) by RIA using 10 microL of plasma. Premature infants had higher secretory burst amplitudes (2.2 +/- 0.13 micrograms/L/min versus 1.4 +/- 0.27 micrograms/L/min, p = 0.02), higher production rates (product of the total number of bursts and the mean mass of GH secreted per burst, 811 +/- 173 micrograms/L/6 h versus 283 +/- 77 micrograms/L/6 h, p = 0.03), and a higher mass of GH per secretory burst (106 +/- 25 micrograms/L versus 38 +/- 11 micrograms/L, p = 0.049) than term infants. The integrated plasma GH concentration exhibited a strong trend toward a higher value in the premature infants (18,100 +/- 800 micrograms/L versus 10,200 +/- 2,700 micrograms/L, p = 0.067).(ABSTRACT TRUNCATED AT 250 WORDS)

Female

The effects of a high-fiber diet on bile acid pool size, bile acid kinetics, and biliary lipid secretory rates in the morbidly obese.

A high-fiber diet has been suggested as one reason for the low incidence of gallstones in some populations. Therefore the authors tested the effects of a high-fiber diet on biliary secretory kinetics and bile salt kinetics in morbidly obese volunteers. Bile salt pool sizes were reduced by 50%, and their half-lives were decreased 70% after the subjects had spent 6 weeks on the high-fiber diet. Bile acid enterohepatic circulation times also were shortened dramatically. However, the lithogenicity of bile did not decrease, and bile remained supersaturated with with cholesterol. Fasting bile samples tended to be even more lithogenic than before the subjects follwed the diet. In these obese subjects, a high-fiber diet failed to reduce the tendency to secrete cholesterol-saturated bile.

Adult

Uptake of K+ by frog gastric mucosa from submucosal side and acid secretory rate.

The K+ content in frog gastric mucosa (K+) was measured as a function of the submucosal K+ concentration ([K+sm]) in the absence of K+ on the mucosal side. The (K+) in HCO3- buffer with 95% O2-5% CO2 gas showed that the removal of external K+ induced a 27% K+ loss from the control value of 5 mM K+sm, that there was no linear relation between (K+) and [K+sm, and that the change in the (K+) versus the [K+sm] was hyperbolic, indicating that there are two different types of K+ in the mucosa: bound and free K+.

Animals

Endoscopic measurement of pancreatic juice secretory flow rates and pancreatic secretory pressures after secretin administration in human controls and in patients with acute relapsing pancreatitis, chronic pancreatitis, and pancreatic cancer.

Secretory flow rates were measured inside the main pancreatic duct during endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute relapsing pancreatitis, chronic pancreatitis, and pancreatic cancer and in controls after intravenous administration of secretin. Peak secretory flow rates in these groups were 5.04 +/- 1.74, 0.71 +/-1.28, 0.60 +/- 1.37, and 4.13 +/- 0.88 ml/min, respectively. Peak secretory pressures were also measured intraductally in patients with acute relapsing pancreatitis and pancreatic cancer and in controls and were 402 +/- 69, 75 +/- 161, and 403 +/- 99 mm pancreatic juice, respectively. Peak secretory flow rates and pressures measured in controls during constant administration of secretin were similar to those measured when secretin was administered as a bolus.

Endoscopy

Foetal-maternal production and transfer of cortisol during the last days of gestation in the guinea-pig.

The metabolism and the rate of transfer of cortisol across the placenta in pregnant guinea-pigs and foetuses were studied by constant intravenous infusions of tritium-labelled cortisol. Estimates of endogenous and radioactive plasma cortisol levels were used to calculate the following parameters at four stages before parturition (days 62, 64, 66 and 67; parturition occurring at day 68): metabolic clearance rate; production rate; adrenal secretory rate; transfer rate from mother to foetus and from foetus to mother; irreversible removal rate; the fraction of cortisol derived from the other in the foetal and maternal vascular compartments; the fraction of secreted and recycled cortisol involved in the transfer. The metabolic clearance rate and the rates of production and secretion of cortisol were higher in the mother than in the foetus between days 62 and 67 of gestation. About 90% of the foetal cortisol was of maternal origin. The fraction of maternal cortisol of foetal origin increased in the last days of gestation.

Anesthesia

Quantitative aspects of insulin secretion and its hepatic and renal removal in sheep.

The secretion of insulin into the portal blood and its removal by the liver and kidneys in conscious fed sheep were determined by simultaneously measuring venoarterial plasma concentration differences and portal, hepatic, and renal plasma flows. The basal secretory rate of insulin was 0.43 +/- 0.03 U/h or 7.8 mU/kg-h. The secretory rate of insulin and the amount of insulin presented to the liver also were altered by 2-h intraportal infusions of glucagon (150 mug/h), insulin (1.17 U/h), and insulin (1.17 U/h) lus glucose (2.2 g/h). Hepatic removal under all conditions was about 50% of the insulin secretory rate, although the extraction ratio was only 0.08. Renal removal was 35% of the insulin secretory rate. The renal extraction ratio was 0.35. During insulin-induced hypoglycemia and also during starvation, the hepatic extraction ratio of insulin increased significantly, but the removal as a percentage of insulin secretion did not change. It appears that in sheep on a maintenance diet the basal secretory rate of insulin is less than that of nonruminant species and that, within physiological limits, the liver disposes of about one-half and the kidney about one-third of the insulin. Other tissues, presumably, remove the remaining 10--20%.

Animals

Bradykinin-induced renal hemodynamic alterations: renin and prostaglandin relationships.

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.

Angiotensin II

The distribution and secretion of kallikrein in some exocrine organs of the rat.

Extractable kallikrein was quantitated in the submandibular, sublingual, and parotid glands and in the pancreas. No kallikrein was detected in the exorbital lacrimal glands and tears. The highest kallikrein concentrations (EU/ml) were in all major salivary gland secretions seen after alpha-adrenergic stimulation, less after beta-adrenergic and least after parasympathetic stimulation. When taking into account the large variations in salivary flow rate, alpha-adrenergic stimulation was in the parotid and particularly in the submandibular gland found to result in the highest kallikrein secretory activity measured by the kallikrein secretory rate(EU/min). This shows that the kallikrein-rich granular tubular cells are selectively activated through alpha-adrenergic sympathetic receptors. The differences observed in the parotid saliva were small and not always statistically significant. However, when cervical nerve stimulation was superimposed upon parasympathetic stimulation, kallikrein secretory rate as well as kallikrein concentration increased. The large individual variations in salivary gland kallikrein content and secretion and the rather small differences observed in kallikrein secretory rate after nervous stimulation of the parotid and sublingual glands, may indicate that the kallikrein-containing striated ducts are also influenced by factors other than the secretory nerves. The kallikrein concentration and secretory rate in urine was studied. A strong positive correlation between kallikrein secretory rate and fluid volume was found in urine but not in saliva.

Animals

In vitro measurement of rate of fluid secretion in rat isolated seminiferous tubules: effects of metabolic inhibitors and ions.

1. An in vitro technique for measuring secretory rate in rat isolated seminiferous tubules is described. 2. The basal rate of fluid secretion was 0-44+/-0-06 nl. cm-1 min-1 (S.E.) (n=21). The rate was found to be inhibited by cooling, addition of metabolic inhibitor 2,4-dinitrophenol (2-5 x 10(-4) M) and removal of glucose from the incubating solution. This indicates that fluid secretion in isolated rat seminiferous tubules is an energy dependent process. 3. Removal of K+ from the incubating medium inhibited the secretory rate in the isolated seminiferous tubules, whereas a fivefold increase in [K+]0 to 23-5 mM had no effect. The secretory rate was also unaffected by the absence of Cl- in the peritubular fluid. 4. Removal of Ca2+ from the peritubular medium caused a rise in the secretory rate. 5. Ouabain (10(-3) M) and acetazolamide (4 x 10(-5) M) caused a fall in the rate of fluid secretion in isolated seminiferous tubules. 6. These results are discussed in relation to the nature of the ionic secretion produced in the tubules.

Acetazolamide