A sensitive radioimmunoassay for atrial natriuretic peptide was used to examine the relation between circulating atrial natriuretic peptide and cardiac filling pressure in normal human subjects, in patients with cardiovascular disease and normal cardiac filling pressure, and in patients with cardiovascular disease and elevated cardiac filling pressure with and without congestive heart failure. The present studies establish a normal range for atrial natriuretic peptide in normal human subjects. These studies also establish that elevated cardiac filling pressure is associated with increased circulating concentrations of atrial natriuretic peptide and that congestive heart failure is not characterized by a deficiency in atrial natriuretic peptide, but with its elevation.

Studies were performed in anesthetized dogs (n = 5) to determine the effects of synthetic atrial natriuretic factor on renal function and renin release. Intrarenal infusion of synthetic atrial natriuretic factor (ANF) (0.3 microgram X kg-1 X min-1) resulted in a transient increase in renal blood flow (126 +/- 8 to 148 +/- 11 ml/min). The duration of this transient vasodilation was 3.1 +/- 0.4 min. Continued infusion was followed by a slight decrease in renal blood flow (126 +/- 8 to 117 +/- 8 ml/min) and an increase in glomerular filtration rate (23.1 +/- 3.5 to 30.7 +/- 1.9 ml/min), with filtration fraction thus being increased (0.19 +/- 0.04 to 0.27 +/- 0.03). These hemodynamic alterations were associated with increases in fractional sodium excretion (0.6 +/- 0.2 to 5.8 +/- 0.8%), fractional potassium excretion (30.8 +/- 9.4 to 56.3 +/- 7.4%), fractional lithium excretion (32.2 +/- 7.1 to 60.3 +/- 5.7%), and fractional phosphate excretion (8.7 +/- 3.5 to 41.6 +/- 11.7%). Intrarenal infusion of synthetic ANF markedly suppressed renin secretion rate (295.5 +/- 84.6 to 17.2 +/- 10.6 ng/min) despite a slight reduction in arterial pressure (123 +/- 9 to 118 +/- 9 mmHg). Our studies demonstrate that synthetic ANF results in a marked natriuretic response that is in part mediated by an increase in glomerular filtration rate. The increase in fractional lithium and phosphate excretion suggests that this factor may also have an action on proximal tubule reabsorption. Further, these studies demonstrate that synthetic ANF markedly inhibits renin secretion.

We studied arterial pressure, portal pressure, inferior vena caval pressure, hepatic interstitial pressure (implanted capsule technique), prenodal lymph flow, and the protein concentration in plasma and lymph in the anesthetized dog under normal conditions and during graded venous hypertension resulting from inferior vena caval occlusion. Under control conditions, portal, interstitial, and inferior vena caval pressures were 7.0, 5.8, and 2.0 mm Hg, respectively, and the lymph-plasma protein concentration ratio was 0.95. During acute venous hypertension, 64% of the inferior vena caval pressure increase was transmitted to the hepatic interstitium, and lymph flow increased 63% for every 1 mm Hg increment in interstitial pressure. The lymph-plasma protein concentration ratio did not change significantly during venous hypertension, indicating that: (1) the reflection coefficient of the sinusoidal wall for the major plasma proteins is close to zero, and (2) protein transport across the microvascular wall is due mainly to bulk flow. Using portal, interstitial, and inferior vena caval pressures as limits for possible values of sinusoidal pressure, our data suggest that (1) control sinusoidal pressure was between 5.8 and 7.0 mm Hg, and (2) approximately 90% of the increase in inferior vena caval pressure was transmitted to the sinusoids. The results indicate that changes in interstitial pressure, lymph flow, and surface transudation rate are major compensatory mechanisms operating in the liver to limit interstitial engorgement during venous hypertension. CireRea

This study examined the importance of changes in renal hemodynamics and renal artery pressure (RAP) in allowing the kidneys to escape from the chronic sodium-retaining effects of aldosterone (Aldo). In five dogs in which RAP was permitted to increase during Aldo infusion (14 micrograms/kg/day), sodium excretion (UNaV) and fractional sodium excretion (FENa) decreased markedly on Day 1 and then returned to control on Days 2 to 4 of Aldo infusion as RAP and glomerular filtration rate (GFR) increased 15 to 19 mm Hg and 20% to 24%, respectively, and remained near these levels during 7 days of Aldo infusion. In seven dogs in which RAP was prevented from increasing with an electronically servo-controlled aortic occluder, UNaV decreased from 256 +/- 3 to 117 +/- 9 mEq/day on the first day and remained at 70 to 80 mEq/day below sodium intake for 7 days of Aldo infusion. Cumulative sodium balance and sodium iothalamate space increased 610 +/- 39 mEq and 3729 +/- 397 ml when RAP was servo-controlled, causing ascites in most of the dogs, while mean arterial pressure did not plateau but continued to rise to 59 +/- 3 mm Hg above control after 7 days of Aldo infusion. When the servo-controller was stopped and RAP was allowed to rise while Aldo infusion was continued, GFR rose to 126% to 136% of control, FENa increased markedly, UNaV increased to 579 +/- 64 mEq/day on the first day, and the dogs returned to normal sodium balance. These data indicate that an increase in RAP, which raises GFR and FENa, is essential in allowing the kidneys to escape from the chronic sodium-retaining action of Aldo and to achieve sodium balance and a stable level of arterial pressure without severe volume expansion and ascites.

Abstract-Pregnancy-induced hypertension m women 1s associated with severe vasoconstrlctlon and reductions m organ blood flow and cardiac output Recent studies have mdlcated that mtnc oxide (NO) synthesis mhlbltlon durmg mid to late gestation m pregnant rats results m severe hypertension and protemuna The purpose of this study was to determme the systemic hemodynamlc and regonal blood flow alterations associated with chronic NO synthesis mhlbltlon m the pregnant rat The study was conducted m four groups of rats virgin rats (n=6), pregnant rats (n=lO), vlrgm rats treated with L-NAME (n=6), and pregnant rats treated with L-NAME (n=l 1) Rats were treated with L-NAME m drmkmg water at a dose of 1 mg/d for a week startmg from day 13 of gestation m pregnant rats or an equivalent time for vlrgms Mean arterial pressure (MAP), cardiac output, total penpheral resistance (TPR), and regional flows were measured by tracmg radlolabeled mlcrospheres m conscious rats Pregnant rats that were given L-NAME showed significantly higher MAP (137+6 versus 96?2 mm Hg), higher TPR (5 08?0 58 versus 2 9020 44 mm Hg/mL/mm/lOO g), and lower cardiac output (87 4?8 4 versus 113 32 11 1 mL/mm) than pregnant controls Chronic NO synthesis mhlbltlon decreased the renal blood flow m pregnant rats at a slgmficantly greater magmtude than m vlrgm rats Significant reductions m reglonal blood flow to the heart, lungs, hver, diaphragm, and skeletal muscles were also observed m pregnant rats treated with L-NAMEThe results of this study mdlcate that NO may play a role m medlatmg the alterations m systemic hemodynamlcs and regional blood flow m late pregnant rats (Hypertension. 1998;31[part 2]:315-320.)Key Words: nitric oxide n blood flow n pregnancy n hypertension D unrig normal pregnancy, maternal blood volume increases markedly, leading to approximately a 30% to 60% increase in cardiac output ' The blood pressure falls despite the increase m cardiac output, mostly because of decreased systemic vascular resistance ' Gestation m humans as well as m different animal models 1s also associated with slgmficant changes m blood flow to different organs and tissues Changes m renal hemodynamlcs include a 20% to 40% increase m GFR that has been correlated with increased RPF 3 Dramatic increases m uteroplacental blood flow also occur during pregnancy to accommodate the Increasing needs of the growing fetus 4-h Furthermore, the pressor responses to exogenously admmlstered vasoconstnctors such as norepmephrme and angotensin-11 are attenuated m pregnant rats',' and humans ' Recent studies have provided evidence that total body NO production as well as regonal production m certain vascular beds 1s increased dunng pregnancy, mdlcatmg that NO could play a role m medlatmg the attenuated vascular reactlvlty and vasodilation durmg gestation " However, the role of NO m mediating the increased cardiac output, decreased vascular resistance, and regional blood flow alterations during pregnancy has not been elucidated PIH, on the other hand, 1s characterized by increased systemi...