C. E. Hall

Comparative Effectiveness of Glucose and Sucrose in Enhancement of Hypersalimentation and Salt Hypertension.

Summary The quantity of 1% saline consumed and the development of salt hypertension in rats were comparably enhanced by addition of either glucose or sucrose in 5% concentration to the drinking solution. Cardiac hypertrophy and lesions were equivalently increased. A curious, and as yet unexplained finding, is that whereas kidney enlargement accompanied consumption of either saline or sucrose-saline solution, such was not the case with glucose-saline. Here the kidney weight did not exceed that of controls, and reno-vascular lesions although present were less pronounced than when other saline solutions were drunk.

Increased vascular response to adrenergic stimulation in rats exposed to cadmium

Adult female rats were injected ip with a low total dose (1–2.25 mg/kg) or a high total dose (7.5 mg/kg) of cadmium, as cadmium chloride with cysteine, given in divided doses spaced over 1–3 wk. At 1–4 wk after administration of high doses of cadmium, anesthetized rats were less responsive to the pressor effect of norepinephrine (1.0–10.0 μg/kg, iv) than were controls. This type of effect has been described previously by other investigators and was not explored further in this study. In contrast to the results in high‐cadmium animals, anesthetized rats of the low‐cadmium group, tested 1–4 wk after exposure, were more sensitive to the pressor effects of norepinephrine (0.1–10.0 μg/kg, iv) than were controls. This increase in sensitivity was no longer apparent in animals tested 16–26 wk later. Neither basal blood pressure in anesthetized animals nor systolic pressure in conscious animals of the low‐cadmium series was different from the corresponding value in controls. Aortic rings isolated from low‐cadmium ...

Prevention of Doca-Salt Hypertension with the Calcium Blocker Nitrendipine

Mononephrectomized female rats on a high sodium intake developed hypertension, hypokalemia, enlarged hearts and kidneys and slight adrenal involution under deoxycorticosterone treatment. Simultaneous administration of nitrendipine (5 mg/kg twice daily) completely prevented hypertension and reduced but did not abolish cardiac enlargement. There was no effect of the calcium slow-channel inhibitor on kidney enlargement, adrenal atrophy or hypokalemia. The ability of the steroid to produce cardiomegaly in the absence of an elevated blood pressure to account for it, tends to confirm the suggestion of other investigators that the steroid may have that effect by a mechanism not involving blood pressure elevation.

Immunity of Fischer 344 rats to salt hypertension

Abstract Female Fischer 344 rats sensitized to the development of salt hypertension by unilateral nephrectomy were given water, 1% NaCl solution or 5% sucrose + 1% NaCl solution to drink. Rats on saline alone drank about twice the fluid volume of those on water, whereas those on the sucrose-saline solution drank four to six times as much. No Fischer 344 rats ever developed hypertension, defined as a systolic pressure exceeding 150 mm Hg, during the six months of the study. However, the group on saline averaged slightly higher arterial pressures than those on water on 13 of the 14 occasions that blood pressure was measured, and the average pressure over the entire experimental period was also significantly increased. The rats on sucrose-saline had a group mean blood pressure which was always significantly higher than that of the group on water and usually greater also than that of the group on saline, and the average pressure over the entire experimental period was significantly augmented above that in either of the other groups. Rats on either of the saline solutions also had a slight but significant degree of heart and kidney enlargement, greatest in the sucrose-saline group, which is attributed to the higher pressures developed, even though they remained within the normotensive range.

Polyvinyl Alcohol Nephrosis Relationship of Degree of Polymerization to Pathophysiologic Effects.

Summary Polyvinyl alcohol of 3 different molecular weights, 37,000, 133,000 and 185,-000, was injected daily and subcutaneously into rats on a high NaCl intake. The lowest molecular weight material was not demonstrated in any of the tissues examined and, over the period studied, produced only mild elevation of blood pressure in a third of the animals which received it. High molecular weight PVA infiltrated a number of organs and tissues. Most prominently it affected renal glomeruli causing swelling and multiplication of endothelial and epithelial cells and often crescent formation. Mild hypertension affected half of the animals and heart, kidneys, liver and spleen were enlarged. Neither polymer caused polydipsia. The intermediate polymer produced severe polydipsia, a nephrotic syndrome associated with ascites and edema, severe hypertension, marked renal damage with severe glomerulonephritis, often hemorrhagic, and widespread cardiovascular lesions. The pathologic effects depend more upon the molecular size than upon chemical structure.

Resistance of Fischer 344 rats to deoxycorticosterone hypertension

Abstract Implantation of one 40 mg pellet of DOCA causes hypertension in the majority of young female Sprague-Dawley rats within three weeks without removal of a kidney or adding salt to the diet. Similar identically-treated Fischer 344 rats remain normotensive. If one kidney is removed and 1% saline is given to drink, the hormone dosage causes hypertension in rats of both strains, although even here Fischer 344 rats develop the disorder more slowly and less severely. It is concluded that for rat strains resistant to mineralocorticoid hypertension, sensitization is necessary for its induction, whereas for susceptible strains it is not. Fischer 344 rats appear to have higher levels of resting serum renin activity than Sprague-Dawley rats, but the relationship that this bears to hypertension susceptibility is unknown.

Aldosterone binding sites in aortic cell cultures from spontaneously hypertensive rats.

Spontaneously hypertensive rats and rats made hypertensive by deoxycorticosterone-salt treatment have in common increased Na+ and K+ permeability and transport in their aortic cells. These changes may be important factors in the development of the hypertensive state and may be mediated by mineralocorticoid binding to intracellular sites in the aorta. Therefore, we examined 3H-aldosterone binding in aortic cell cultures from spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Vascular corticoid binding sites in the two strains were compared by Scatchard analysis of Kd and Bmax, pH and temperature stability, and subcellular binding. By all of these criteria normotensive rats. These results indicate that the underlying genetic defect in spontaneous hypertension is not an intrinsic cellular defect which alters mineralocorticoid binding in the aorta.

Prevention of spontaneous and glucocorticoid hypertension in rats by nisoldipine

The effect of daily treatment (sometimes interrupted) with the calcium blocker nisoldipine at two different dose levels, one double the other, on the development of spontaneous hypertension in the rat was evaluated. Both doses prevented development of the disorder during daily administration, but when treatment was stopped the same degree of hypertension as in controls quickly developed. Resumption of treatment caused blood pressure to fall to or towards normal again. The higher dose caused a more rapid and greater fall than the lower, and allowed a lesser pressor response when it was discontinued. The drug had no effect on growth, and the only consistent hematological effect was a slight thrombocytosis. Daily treatment at a single dose level slightly reduced normal blood pressure and prevented cortisone hypertension. Serum renin activity was unaffected by nisoldipine but was elevated by cortisone treatment: nisoldipine increased aldosterone levels, but not when cortisone was also given.

Decreased aldosterone receptor affinity in aortic cells from the Fischer 344 rat.

The Fischer 344 rat strain represents a uniform population that is immune to salt induced hypertension and resistant to mineralocorticoid hypertension. We have compared aldosterone binding in aortic cells cultured from salt-resistant Fischer 344 rats to that from salt-sensitive Wistar-Kyoto controls for aldosterone binding. Aortic smooth muscle cells of both strains contain two classes of aldosterone binding sites: corticoid receptor I with high affinity and low capacity and corticoid receptor II with low affinity and high capacity. The corticoid receptor I of Fischer 344 rats has a significantly (P less than 0.001) lower affinity than that of age and sex-matched Wistar-Kyoto controls, but the binding capacity was the same. There was no difference between the strains in the affinity or binding capacity of corticoid receptor II. These results indicate that mineralocorticoid binding may be important in susceptibility and resistance to hypertension and support the contention that mineralocorticoids regulate blood pressure in part by direct action on vascular smooth muscle cells.

Inhibition of Doc-Salt and Adrenal-Regeneration Hypertension With the Calcium Blocker Nifedipine

When nifedipine was given to rats at a dosage of 0.3 mg/kg, the blood pressure fell and heart rates rose slightly in normotensive controls, but both changes were more marked in rats with DOC-salt hypertension, the magnitude of the drop in mm Hg being progressively greater as hypertension evolved. Tachycardia also tended to increase, but became somewhat erratic once hypertension was established. Both changes were relatively constant and equivalent when expressed as a percentage of the initial value. Nifedipine given by minipump at a dosage of 8 mg/ml proved able to prevent or modulate, adrenal-regeneration hypertension, but not DOC-salt hypertension. However, in the latter, when the pumps were discontinued and a 1 mg/kg/day injection schedule was substituted, blood pressure fell in nifedipine-treated and rose in untreated rats. The latter dosage had a greater effect on blood pressure and heart rate of normotensive rats than 0.3 mg/kg.