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A synthetic oligonucleotide probe complementary to messenger ribonucleic acid (mRNA) encoding for the C-terminal portion of atrial natriuretic factor (ANF) has been used to study the expression of the ANF gene in rat myocardium. Four experimental models were studied: binephrectomy (for 48 h); ligature of both ureters (for 48 h); deoxycorticosterone acetate-salt (for 3 wk); and aortocaval fistula (for 2 wk). Analysis of atrial RNA by gel-blot hybridization detected a single band, corresponding in length to that of mRNA coding for ANF. Such an mRNA was also detected in ventricular RNA but was 1/50th as abundant. In the four experimental groups ANF mRNA was increased significantly as compared with controls. In all rats there was no significant difference in the ANF mRNA content between the left and the right atrium. Each experimental condition was accompanied by a highly significant increase in ANF gene expression in the left ventricle, where all of the ventricular tissue could be recruited and with a negative gradient from the base to the apex of the left ventricle. These data were confirmed by in situ hybridization. Thus all of the atrial and ventricular myocardium can express the ANF gene. Recruitment increases in response to passive stretch of the cardiac chambers.

The preferential release of the neurohypophyseal hormones vasopressin and oxytocin by appropriate stimuli implies that neurons secreting each hormone receive different afferent connections and may therefore contain membrane receptors for different neurotransmitters. Since electrophysiological studies on rat supraoptic nucleus (SON) neurosecretory neurons suggest that the activated vasopressin-secreting neuron may be selectively identified by a phasic activity pattern, extracellular recordings were performed in pentobarbital anesthetized male Sprague-Dawley rats to compare the responses of 59 phasically-active SON neurosecretory cells to several neurotransmitter candidates endogenous to SON and applied by microiontophoresis. Among excitatory agents, most SON cells demonstrated a brisk depolarization to aspartate and glutamate; quiescent cells could also be induced into phasic activity by continuous application of either amino acid with low currents. During applications of acetylcholine and nicotine, phasically active neurons demonstrated elongated periods of continued activity, but without an increase in overall firing frequency, suggesting a possible mechanism for cholinergic enhancement of vasopressin release. In contrast, norepinephrine (NE) exerted an opposite action by either terminating a burst of activity prematurely or decreasing the number of action potentials per burst; some cells displayed a prolonged arrest of phasic activity for several minutes following NE applications. This mechanism of action could explain any inhibitory effect of NE on vasopressin secretion. We observed no apparent tachyphylaxis to repeated NE applications. GABA applications also terminated phasic activity prematurely, but cell firing resumed within seconds of removal of the application currents. Leucine enkephalin exerted a weak depressant action on the excitability of a small percentage of phasically-active SON neurons. For further comparison, we tested these agents on 18 continuously-active (possible oxytocin-secreting) SON neurosecretory neurons. Most of these neurons demonstrated changes in excitability similar to that noted on phasically-active cells; however, the duration of drug action seldom outlasted the period of its application. One exception was the observation that acetylcholine, but not nicotine, depressed the firing of a portion of the continuously-active SON neurosecretory cell population. These extracellular observations provide preliminary evidence of differences in the neuropharmacological properties of SON putative vasopressin- and oxytocin-secreting neurons that may be better clarified with detailed intracellular measurements.

Using unanaesthetized monkeys, experiments were performed to examine the effects of haemorrhage on the liberation of arginine vasopressin (AVP). Haemorrhages of 10%, 15% or 20% total blood volume were performed via a catheter with its tip in the abdominal vena cava. A catheter in the left internal jugular vein was used for blood sampling. Arterial blood pressure was monitored via a catheter whose tip resected in an iliac artery. The monkeys showed no signs of discomfort from this catheterisation. Blood samples for AVP assay were taken at different times from 0-90 min after the end of the haemorrhage. At the end of the experiment, blood removed was reinfused. Results show that haemorrhage resulted in liberation of AVP, but only if there was a fall in arterial blood pressure. AVP release occurred more readily as the total volume of blood withdrawn increased, but the absolute rise in hormone concentration was not related to the total volume of blood withdrawn. However, comparing the area under the curve of mean arterial blood pressure with that for AVP concentration showed the two to have a significant exponential relationship. It is concluded that, as in other species, haemorrhage is a potent stimulus for AVP liberation in the monkey. However, in contrast to some other species, the fall in arterial pressure seems to be the prime stimulus rather than hypovolemia per se.

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