A male rat with spontaneously high systolic blood pressures of 150 to 175 mmHg persisting for more than one month and a female rat with blood pressures slighty above the average, 130 to 140 mmHg, were selected from among 68 Wistar strain rats in normal condition and mated to obtain F1 rats. Of these F1 rats, males and females with hypertension (blood pressure exceeding 150 mmHg) persisting for more than a month (mostly over 2 months) were mated to produce F2 rats. The procedure was repeated to obtain F3, F4, F5 and F6 rats totaliag 380 animals. The weights and blood pressures (by the tail-water-plethysmographic method) were measured once weekly biginning at 4 weeks of age, and the results can be summarized as follows : 1. In body weight, the F rats showed little difference from the normal controls. 2. The blood pressures of F rats rose with age and from generation to generation, increasing significantly above those of normotensive controls of the same age after 20 weeks of age among female F1, after 15 weeks among male F1 and also male and female F2, and after 10 weeks among all F3 to F6 rats. E. g., the average systolic blood pressure of F5 at 25 weeks of age was 206+__-18.5 mmHg in the male and 193+__-20.5 mmHg in female rats. The blood pressures of normotensive controls remained at 131 to 136 mmHg in the male and 130 to 135 mmHg in female rats after 10 weeks of age. 3. Many F rats showed spontaneous hypertension. The incidence of the spontaneous occurrence of hypertension increased, and the development of hypertension occurred at younger ages from generation to generation. All of the F3 to F6, rats developed spontaneous hypertension within 15 weeks of age. Severe hypertension with blood pressures exceeding 200 mmHg began to observed among F2. The incidence of such severe hypertension increased with each generation, so that among male animals it inceased from only 9% in F2 to 35% in F3, 42% in F4, and 56% in F5, and in female animals from 3% in F2, 16% in F3, 33% in F4, and 37% in F5. The authors have named this Wistar strain of rats with spontaneous occurrence of hypertension as "spontaneously hypertensive rats (Okamoto-Aoki)". 4. The blood pressures of β-line rats from parents with very high blood pressures were significantly higher than among α-line rats from parents with moderately high blood pressures at the same age. 5. There was no difference in the blood pressures of offsprings resulting from inbreeding and those from cross breeding. The male blood pressure averaged about 10.6 mmHg above the female value in spontaneous hypertension, and hypertension developed at lower ages in the male. 6. It is a question for future study whether the spontaneous hypertension induced in rats in this Study is comparable in characteristics with essential hypertension in man.

Development of a Strain of Spontaneously Hypertensive Rats

Development of a strain of spontaneously hypertensive rats.

PATHOLOGIC conditions characterized by inflammation and fibrinoid necrosis have constituted a perplexing and controversial subject in the medical literature for many years. The tendency in recent d...

Periarteritis nodosa and other forms of necrotizing angiitis

The primary adrenal cortical steroid hormones, aldosterone, and the glucocorticoids cortisol and corticosterone, act through the structurally similar mineralocorticoid (MR) and glucocorticoid receptors (GRs). Aldosterone is crucial for fluid, electrolyte, and hemodynamic homeostasis and tissue repair; the significantly more abundant glucocorticoids are indispensable for energy homeostasis, appropriate responses to stress, and limiting inflammation. Steroid receptors initiate gene transcription for proteins that effect their actions as well as rapid non-genomic effects through classical cell signaling pathways. GR and MR are expressed in many tissues types, often in the same cells, where they interact at molecular and functional levels, at times in synergy, others in opposition. Thus the appropriate balance of MR and GR activation is crucial for homeostasis. MR has the same binding affinity for aldosterone, cortisol, and corticosterone. Glucocorticoids activate MR in most tissues at basal levels and GR at stress levels. Inactivation of cortisol and corticosterone by 11β-HSD2 allows aldosterone to activate MR within aldosterone target cells and limits activation of the GR. Under most conditions, 11β-HSD1 acts as a reductase and activates cortisol/corticosterone, amplifying circulating levels. 11β-HSD1 and MR antagonists mitigate inappropriate activation of MR under conditions of oxidative stress that contributes to the pathophysiology of the cardiometabolic syndrome; however, MR antagonists decrease normal MR/GR functional interactions, a particular concern for neurons mediating cognition, memory, and affect.

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The multifaceted mineralocorticoid receptor.

Unilateral nephrectomy in hypertensive disease.

0 NE of the difficulties involved in determining experimentally the exact r8le which the kidney plays in the pathogenesis of hypertension has been the impossibility of ablating this organ without introducing the fatal effects of interfering with its normal excretory function. For this reason, it has been impossible to apply the simple experimental procedure of extirpation which has aided so much in the elucidation of the function of other organs. It is, in fact, generally assumed that bilateral nephrectomy causes no change in the blood pressure. However, animals subjected to this procedure in the past have survived for such relatively short periods and were in such poor condition that any conclusion as to the effect of nephrectomy on the blood pressure based on observations of such animals is not convincing.

Role of the kidney in pathogenesis of hypertension as determined by a study of the effects of bilateral nephrectomy and other experimental procedures on the blood pressure of the dog.

Papillary necrosis of the kidney is reported infrequently in the literature and is only rarely diagnosed during life. During the past year, we have encountered 3 morphologically proved cases as well as others in which such proof is lacking but which clinically were apparently in accord with this diagnosis. Since the original description of this condition by Friedreich in 1877,1papillary necrosis of the kidney (necrotizing renal papillitis) has been considered by most observers as a manifestation of pyelonephritis which occurs usually as a complication of diabetes mellitus.2However, as shown by Edmondson, Martin and Evans3in their recent review of this subject, 40 per cent of their cases occurred in nondiabetic patients with urinary tract obstruction. Among the few experimental observations are those of Mallory, Crane and Edwards,4who produced the lesion in rabbits by ligating one ureter and subsequently injecting pathogenic organisms intravenously. Our

PAPILLARY NECROSIS OF THE KIDNEY: A Clinical and Experimental Correlation

THE OCCURRENCE of acute oliguria or anuria as a complication of incompatible blood transfusions, after prolonged arterial hypotension or following intoxication with sulfanilamide derivatives, mercuric chloride and other compounds and the recognition that the resultant renal insufficiency may be temporary has stimulated interest in the use of an artificial kidney or peritoneal lavage in the treatment of such a condition. The reports in the current scientific literature, as well as in the lay press, describing the use of these measures give an erroneous impression of their wide field of usefulness as well as of the success attributed to their application. Our investigations on the use of the artificial kidney during the past year have demonstrated many inherent dangers which previous investigators have failed to note. We have also treated successfully patients in acute renal failure by the simpler and safer procedures to be discussed later. REVIEW OF THE LITERATURE

John Vanatta

Papers

Role of the kidney in pathogenesis of hypertension as determined by a study of the effects of bilateral nephrectomy and other experimental procedures on the blood pressure of the dog.

PAPILLARY NECROSIS OF THE KIDNEY: A Clinical and Experimental Correlation

Acute renal insufficiency; a comparison of the use of an artificial kidney, peritoneal lavage and more conservative measures in its management.

Effect of desoxycorticosterone acetate on the peripheral vascular reactivity of dogs.

32. Use of the artificial kidney