Nick C. Trippodo

Renal response to acute volume overload in conscious rats with atrial appendectomy.

The presence of volume receptors and a potent natriuretic factor (ANF) in mammalian cardiac atria strongly suggests a central role of the atria in extracellular fluid volume regulation. ANF is stored within granules in atrial appendages, and their removal could alter the response to volume overload. We tested this hypothesis in conscious Wistar rats two weeks after sham operative or atrial appendectomy. The results indicate that removal of the atrial appendages significantly reduced their urinary excretion of water, sodium and potassium during the first hour following acute volume overload. It is concluded that atrial appendectomy alters the ability of rats to handle acute volume overload possibly through a reduction in the ANF available for release.

Atriopeptin III does not Alter Cardiac Performance in Rats

The effects of atriopeptin III (APIII) on systemic haemodynamics were examined in 12 anaesthetized rats. Five minutes following intravenous injection (i.v.) of 10 micrograms/kg APIII, cardiac output CO, measured by electromagnetic flowmetry, stroke volume and mean arterial pressure (MAP) decreased by 14, 13 and 8% (P less than 0.05), respectively, and total peripheral resistance (TPR) increased by 10% (P less than 0.05). Heart rate (HR) and left ventricular end-diastolic pressure (LVEDP) did not change. In order to examine cardiac performance, whole blood was infused into three groups of 12 rats each receiving either no injection, APIII (10 micrograms/kg i.v.) or APIII (10 micrograms/kg i.v.) plus a continuous infusion of phenylephrine to increase MAP to pre-injection levels. Cardiac performance curves did not differ among the three groups. These data indicate that the immediate decreases in MAP and CO produced in rats by a maximum natriuretic bolus dose of APIII were not mediated by a negative myocardial inotropic effect.

Rat platelets activate high molecular weight atrial natriuretic peptides in vitro.

Evidence suggests that the more biologically active low molecular weight forms (less than 10,000) of rat atrial natriuretic peptides are proteolytically derived from a less active precursor of higher molecular weight. Conversion and activation could occur within the myocyte as well as during circulation. The present study found that in vitro rat blood and platelets were capable of converting the high molecular weight atrial natriuretic peptides (greater than 10,000) to low molecular weight atrial natriuretic peptides within minutes and that enhanced biological activity attended the conversion. Rat high molecular weight peptides were partially purified by gel filtration, lyophilized, and reconstituted in Krebs-Ringer bicarbonate buffer. One milliliter of fresh rat blood was incubated with the high molecular weight peptides at 37 degrees C for 2 minutes. After centrifugation, the supernatant was fractionated on Sephadex G-75. Natriuretic activity was determined by bioassay in anesthetized rats. In contrast to the results following incubation of high molecular weight peptides in Krebs-Ringer bicarbonate buffer alone, which showed that 95% of the natriuretic activity remained in the high molecular weight peptide region, the natriuretic activity of the blood-treated high molecular weight peptides eluted almost exclusively in the low molecular weight peptide region, which indicates conversion. Blood was separated into plasma, erythrocytes, lymphocytes, and platelets. Conversion of high to low molecular weight peptides occurred only after incubation with platelets. Compared with control high molecular weight peptides, rat platelet-treated high molecular weight peptides had significantly greater activity in relaxing histamine-contracted rabbit aortic smooth muscle (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Dehydration attenuates the acute natriuretic response to rat atriopeptin III (rAPIII).

The acute natriuretic response to atrial peptides (AP) is highly variable in anesthetized rats, and some rats are unresponsive. To determine if this response to AP was affected by dehydration, we measured hematocrit, plasma volume, and natriuresis (delta UNaV) after intravenous injection of 3 micrograms/kg of rat atriopeptin III (rAPIII) in anesthetized rats deprived of water for 0, 12, 20, 29, 44, and 68 hours. Data were compared with those from rats receiving 1.5 mg/kg furosemide (FU) after 0 and 68 hours without water. There were 10- and 3-fold decreases in delta UNaV following rAPIII and FU injection after 20 and 68 hours without water, respectively. Hematocrit increased and plasma and total blood volumes decreased after 12 hours of dehydration. Plasma volumes and delta UNaV were correlated (r = 0.64, p less than 0.05; r = 0.75, p less than 0.001) in the combined groups receiving rAPIII (n = 30) and FU (n = 10), respectively. These results demonstrate that a relatively short period of water deprivation (WD) and the resulting hemoconcentration in rats decreased their acute natriuretic response to diuretics. Thus, differences in water intake may account for some of the large variation in delta UNaV after exogenous administration of rAPIII.

Rat atrial natriuretic peptides inhibit oxygen consumption by rat kidney.

The inhibitory effect of high and low molecular weight native and synthetic rat atrial peptides on oxygen consumption in isolated rat kidney mitochondria and slices was measured. Oxygen consumption by mitochondria was measured in the presence of succinate and/or adenosine diphosphate, furosemide, and low and high molecular weight native and synthetic rat atrial peptides. After the addition of succinate, adenosine diphosphate limiting respiration (State 4) increased in the presence of low, but not high, molecular weight native rat atrial peptides. Furosemide caused a significant decrease in State 4 respiration (p less than 0.001). Angiotensin II and arginine vasopressin did not alter State 4 respiration. The rate of oxygen consumption after the addition of saturating adenosine diphosphate in the presence of saturating succinate (State 3 respiration) was reduced by low and high molecular weight native rat atrial peptides. Furosemide completely blocked oxygen consumption after the addition of adenosine diphosphate. Oxygen consumption was unchanged by trypsin treated (natriuretically inactive) low molecular weight rat atrial peptides and ventricular protein extracts of high and low molecular weight native rat atrial peptides. Synthetic and low molecular weight native rat atrial peptides had similar effects on mitochondrial oxygen consumption. Low molecular weight native and synthetic rat atrial peptides decreased the adenosine diphosphate to oxygen ratio, and these peptides, as well as furosemide, also induced mitochondrial swelling; none of the other rat atrial peptide combinations nor angiotensin II produced this effect. In kidney slices, basal oxygen consumption (without substrates) was stimulated by succinate.(ABSTRACT TRUNCATED AT 250 WORDS)