Miyoshi Nakashima

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.

Morphological assessment of vasoconstriction and vascular hypertrophy in sustained hypertension in the rat

Abstract Measurements of individual smooth muscle cells and of the media were made in blood vessels fast-frozen in vivo during norepinephrine administration, in active DOCA-induced hypertension, and in sustained post-DOCA (metacorticoid) hypertension. In acute vasoconstriction, the cells shorten and thicken without change in their surface envelope. Cell volume increases and this increase becomes pronounced as length decreases beyond 70%. The cross-sectional area of the media as a whole does not change. Active DOCA hypertension is dominated by an increase in the surface and volume of individual cells and no shortening was observed. The area of the media is increased in consequence and encroaches on the lumen. In metacorticoid hypertension, no cell hypertrophy was observed but cells were shortened. The area of the media was unchanged but the shortened cells narrowed the lumen in proportion to the degree of elevation of blood pressure. Whether this vasoconstriction is active or structural cannot be resolved. These studies demonstrate that vascular hypertrophy is not a necessary condition of the sustained hypertensive state.

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.

Lithium Substitution Analysis of Na and K Phases in a Small Artery

Cell Na in the rat tail artery was measured by replacing all extracellular Na with Li at 2°C. Water was partitioned with 14C-sorbitol as the marker. The binding capacity of the cytoplasm wa

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.

Further observations on “sustained” hypertension in the rat☆

Abstract Rats subjected to a short period of intensive treatment with DCA may develop a sustained hypertension after cessation of treatment. The percentage of rats which remain hypertensive appears to depend on the severity of treatment. Although a renal functional impairment is demonstrable in the post-DCA period, it occurs equally in those rats which do not sustain the hypertension and in those which do. The renal handling of sodium and potassium in post-DCA animals differs slightly from that of control animals, but bears no observable relation to the presence or absence of hypertension. Histologic study of both kidneys and adrenals fails to reveal any difference between normotensive and hypertensive animals. The presence of a sustained hypertension, hitherto reported on the basis of indirect blood pressure observations, has been fully confirmed by direct electromanometry.

Single sample analysis with the sodium electrode

Abstract The cannula-type metal-connected electrode is a practical device for the measurement of sodium in single aliquots of biological materials such as blood or urine. Measurements can be carried out with either diluted or undiluted samples using simple devices to present the solutions to the sensing membrane. Since the electrode responds to activity rather than concentration, ion binding has an important bearing on the analytical result. Evidence suggesting significant sodium binding in plasma is presented.

Sodium Gradient and Renoprival Hypertension in the Rat

Following nephrectomy in the rat blood pressure rises while the extracellular fluid volume increases, sodium concentration falls and potassium rises. These changes (without the potassium rise) can be mimicked by simple hyperosmotic loading while the reverse can be induced by dehydration. The rise in blood pressure is not due to either expansion of the extracellular space or the fall in sodium concentration alone but probably to the resultant decrease in the Nao/Na1 gradient.

Biphasic Effect of Pitressin on Sodium Tolerance in the Hypertensive Rat

The effect of a large dose of Pitressin (2 iu subcutaneously) on Na and water excretion under load was studied in rats made hypertensive by DCA. This dose is calculated to be within the upper limit of physiological secretion by the neurohypophysis. The excretion pattern was determined during the 4 1/2 hours following gavage with 100 mg of NaCl in 3 cc of water, both for the period immediately following Pitressin administration and for the period 3 hours after administration. These two periods were selected as corresponding to the pressor and depressor phases of Pitressin action, respectively. The procedure was carried out after one, four and eight daily injections of Pitressin. The selection of control and hypertensive animals was based on a preliminary blood pressure determination obtained by direct electromanometry from the femoral artery. The experiments demonstrated that Pitressin at this dose level has a biphasic action on the handling of Na and water as it has on blood pressure. The first phase consists of a limited tendency to accentuate the already accelerated rate of Na and water excretion found in the hypertensive state. This first effect was not obtained after eight injections. The second phase is characterized by a marked decrease in Na and water excretion which appears to be independent both of the antecedent rate of Na and water loss and of the number of injections.