Constance L. Friedman

Sodium Gradient, Smooth Muscle Tone, and Blood Pressure Regulation

Rat colon strips respond to an acute reduction of sodium concentration in the medium (Nao) by an immediate increase in tension, followed by relaxation to the basal tension as the tissue equilibrates. Following equilibration in low Nao the responsiveness to drug-induced contraction is increased, while in high Nao it is decreased. A contraction cycle, variously induced, can be aborted by the acute addition of sodium to the medium. The applicability of these findings to vascular smooth muscle in the whole animal can be demonstrated by appropriate acute sodium infusions. The effects in all cases can be referred to sodium, although modified by the anionic component of the salts used. The results are considered to support the view that smooth muscle tension is governed in part by the concentration gradient Nao/Nai and the theoretic implication of this for chronic hypertensive and hypotensive states is developed.

Increased erythrocyte permeability to Li and Na in the spontaneously hypertensive rat

Red blood cells incubated in a physiological medium in which Li replaces Na (LiPSS) gain Li in exchange for Na and K. The rate of Li uptake is modestly but significantly increased in the spontaneously hypertensie rat (SHR) at 37°C and at 22°C. The slow rate of Na gain and K loss during cooling at 2°C was about doubled in unmodified whole blood samples from the SHR.

Cell Na and K in the rat tail artery during the development of hypertension induced by desoxycorticosterone acetate.

Summary An increase in total Na, due in large part to an increase in cell Na, was measured in the freshly excised rat tail artery during the course of DOCA-saline treatment. Since this change was associated with a fall in cell K, was first observed at 2 weeks, coincident with the rise in blood pressure, and was not sustained during subsequent immersion of the artery at zero pressure, it probably reflects the high in vivo intravascular pressure. In the incubated artery, cell Na is significantly reduced early n the course of treatment, while cell K falls late. Thus, Na transport in the artery is under direct attack from the start, but it is suggested that this leads to hypertrophy rather than to vasoconstriction.

Cationic Shifts and Blood Pressure Regulation

The effects of Pitressin and norepinephrine on movements of sodium, potassium, and water into and out of the intracellular compartment were measured in bilaterally nephrectomized rats using inulin as a measure of extracellular fluid volume. Observations were made from 0.5 to 7 min. following injection of the test substances. Pitressin causes a movement of sodium and water into cells and the extrusion of potassium during the pressor plase of its action. These effects were observed at 0.75 and 1.5 min. after the injection of 30 or 60 mU. The reverse movements were observed during the subsequent return of the blood pressure towards normal. A secondary shift of sodium into cells was observed at 5 min. Norepinephrine caused similar shifts in sodium, water, and potassium in relation to its blood pressure effects. These were more rapid in onset than those induced by Pitressin. Our operational theory is that the regulation of the blood pressure depends, inter alia, on the “sodium transfer systems” broadly defined, which govern the rate of entrance and extrusion of sodium, water and potassium in smooth muscle cells.

The pattern of recovery of renal function following renal artery occlusion in the dog.

The pattern of recovery of renal function following two hours of complete ischemia was studied in a series of dogs. A marked functional ischemia persisted for several hours after release of the clamp, but restoration of blood flow was substantially complete in 24 hours. Other renal functions returned slowly over a period of weeks, reflecting the rate of repair of damaged tubules. Two important phases of recovery are thus to be considered: (a) a brief but significant period of continuing ischemia immediately following the trauma, and (b) a period of slow repair of those nephrons damaged but not destroyed in the first phase of the insult.

Effect of aldosterone and hydrocortisone on sodium in red cells.

Natrium- und Kalium-Plasmakonzentrationen und Hamatokritwerte wurden in menschlichem Blut nach Beifügung von kleinen Mengen Aldosteron nach 2-, 4-, 6-oder 24stündiger Kühlung oder nach ½-, 1-, 2- oder 3stündiger Erwärmung gemessen. Aldosteron vermindert die Plasma-Natriumzuwachsrate bei Erwärmung und anscheinend auch die Plasma-Natriumverminderungsrate bei Kühlung. Hydrokortison ergab das gleiche Resultat bei Erwärmung, während seine Wirkung bei Kühlung noch nicht abschliessend untersucht wurde.

Use of glass electrode for measuring sodium in biological systems.

Summary Development of a sodium glass-to-silver electrode for biological use has been described. The instrument is simple and particularly useful for continuous recording of small changes in sodium concentration, both in static and in flowing systems. As such, it should be applicable to a wide variety of studies.

Prolonged treatment with posterior pituitary powder in aged rats

Abstract A suspension of posterior pituitary powder in saline was administered subcutaneously three times weekly for 6 months to a group of old rats, 24 months of age at the start of the experiment. A matched group was given a trace amount of aldosterone as well. Average lifespan compared with that of untreated old controls was increased and general condition, judged by observation, was improved by treatment. The dose of posterior pituitary powder was modest since it did not affect body weight and in a 48-hr balance study produced only a minimal antidiuretic effect. Even so, it was quite sufficient to produce a significant improvement in the ability of the indirectly stimulated gastrocnemius to perform work as measured isometrically. Further, treatment was quite sufficient to suppress to a significant degree the increase of weight of kidney, heart, adrenal and pituitary ordinarily associated with aging in the rat. No additional effect was produced by the trace supplement of aldosterone since the benefits obtained were the same in both treated groups. In an earlier experiment a slightly larger dose of aldosterone was found to be toxic.

Extrarenal Effects of Intravenous Pitressin in Nephrectomized Rats

Using inulin as indicator of the extracellular fluid volume, the effects of Pitressin on the movements of sodium and potassium were studied in the nephrectomized rat together with simultaneously determined direct blood pressure values. Pitressin caused a movement of sodium and water into cells coupled with the extrusion of some potassium during the phase of blood pressure elevation. The beginning of the phase of blood pressure decline coincided with a rapid shift of potassium into cells while the sodium and water acquired by cells in the early phase were gradually extruded. These shifts were demonstrable with as little as 10 mU. of Pitressin intravenously while the maximal effect occurred in the 30 to 50 mU. dose range. These effects may account for many of the changes observed with Pitressin in the intact animal and also may have some bearing on blood pressure homeostasis.

The action of ouabain on the smooth muscle cells of the rat tail artery.

Summary The transmembrane Na and K gradients of the smooth muscle cells of the rat tail artery are discharged about twice as fast in the absence of external K ions as in the presence of ouabain although a 1:1 exchange is involved in both cases. In large part, this observation reflects the fact that cell Na remains lower and cell K higher after prolonged incubation in a normal medium with maximal ouabain than in a K-free medium. These experiments still do not wholly exclude the possibility that changes in membrane permeability may also be involved. The authors are indebted to Miss Maryette Mar for expert technical assistance.