Adrenal-enucleated Rats Research Articles

Changes in the potentiation effect of [D-Ala2, Met5]-enkephalin on pressor responses to l-adrenaline in adrenal-enucleated rats

Physiological significance of colocalization of enkephalin and adrenaline in the adrenal medulla was studied by examining pressor responses to concomitant administration of [D-Ala2, Met5]-enkephalin (100 micrograms/kg, s.c.) and l-adrenaline (50 micrograms/kg, s.c.) in adrenalenucleated rats. The adrenal medulla of Wistar-Imamichi rats was removed at 3 weeks (3WAdMx) or 12 weeks (12WAdMx) of age. Control rats were sham-operated. Blood pressure (BP) was measured by the tail-cuff method. 1) A single s.c. injection of enkephalin induced a marked rise in BP at 10 min in control male and female and the 3WAdMx-male rats, whereas the 3WAdMx females showed only a 5 mmHg increase at its maximum in the BP following enkephalin administration. 2) In the control male and female rats, the 5 min pretreatment with enkephalin enhanced the pressor response to l-adrenaline, and the pressor effect of enkephalin plus l-adrenaline was suppressed by pretreatment with naloxone (2.5 mg/kg, s.c.). On the other hand, in the 3WAdMx male and female rats, the pressor effect of l-adrenaline was almost completely suppressed by pretreatment with enkephalin. Moreover, pretreatment with naloxone resulted in an increase in BP after administration of enkephalin plus l-adrenaline in the 3WAdMx female rats. 3) In contrast to the control female rats, the pressor effect of enkephalin plus adrenaline was also enhanced by pretreatment with naloxone in the 12WAdMx female rats. The results suggest that the lack from immature age of catecholamine and enkephalin which originate from the adrenal medulla appears to alter the responsiveness of the BP regulatory system to exogenous catecholamine and enkephalin in the rat.

Reduced pressor response to l-adrenaline following enkephalin administration in adrenal-enucleated rats and its transmission to the first generation offspring.

Reduced pressor response to l-adrenaline following enkephalin administration in adrenal-enucleated rats and its transmission to the first generation offspring.

The Effects of Adrenalectomy, Adrenal Regeneration, and Renal Irradiation on Blood Pressure

Adrenalectomized, adrenal-enucleated and adrenal-intact rats were sham-irradiated or received an x-ray dose of 1100 rad bilaterally to temporarily exteriorized kidneys. Systolic blood pressures were measured at 10, 25, 40, 60, and 80 days after irradiation. At 100 days after irradiation the rats were sacrificed for gross pathologic examination and renal histopathologic studies of the kidneys. Adrenalectomy alone caused a significant drop in blood pressure which persisted throughout the experiment; adrenal regeneration in adrenal-enucleated rats or in those adrenalectomized rats in which adrenal tissue regenerated caused a significant increase in systolic blood pressure after 80 days postirradiation. Irradiation of adrenal-intact, adrenal-regenerating, or adrenalectomized rats did not cause significant elevation of blood pressure in comparison with that of the corresponding nonirradiated controls. Rats showing subtle renal histological changes usually showed somewhat higher blood pressures than rats showing no renal histological changes; a few rats which became severely hypertensive showed considerable histopathological changes in kidneys and other organs.

Adrenal Mitochondrial and Serum Corticosteroid Studies in RatsResistant to Adrenal-Regeneration Hypertension (ARH)

Female rats of the Wistar-Furth (W/Fu) strain appear to be resistant to the development of adrenal regeneration hypertension. At a time period, after adrenal enucleation, when Holtzman female rats had elevated serum 11-deoxycorticosterone levels and were hypertensive, none of the W/Fu rats became hypertensive. In vitro adrenal studies after quiescent kills of W/Fu rats indicated that cholesterol side chain cleavage activity was greater in mitochondria from regenerating adrenals than from controls. Both serum deoxycorticosterone and corticosterone levels were significantly greater in the adrenal-enucleated group. These studies were repeated in animals which were given a standard ether anesthetic stress. Ether stress increased cholesterol side chain cleavage activity comparably in control and adrenal-enucleated rats and also increased their serum deoxycorticosterone and corticosterone levels. Adrenal-enucleated Wistar-Furth rats had higher serum deoxycorticosterone levels than controls, whereas controls had higher serum corticosterone levels than the adrenal-enucleated group after the ether stress. These results indicate that although the adrenal-enucleated W/Fu rats have increased serum deoxycorticosterone levels, none of these rats develop frank hypertension. This suggests a resistance to deoxycorticosterone-induced hypertension in this strain of rat.

Effect of a spironolactone derivative (SC 14266) on Plasma renin activity in adrenal regeneration hypertension.

The effects of treatment with a spironolactone derivative (SC 14266) for 9 experimental weeks on blood pressure and plasma renin activity (PRA) were investigated in unilaterally nephroadrenalectomized rats drinking 1% saline ("unilater nephrectomy"), unilaterally nephroadrenalectomized and contralaterally adrenal-enucleated rats drinking 1% saline ("adrenal enucleation") and intact rats drinking tap water ("normal"). The development of hypertension in "adrenal enucleation" rats was prevented by treatment with SC 14266 and the drug did not significantly affect the blood pressure in either "unilateral nephrectomy" or "normal" rats. SC 14266 did not influence a low level of basal PRA and the blunted response of PRA to furosemide administration in either "unilateral nephrectomy" or "adrenal enucleation" rats. On the other hand, PRA after furosemide administration in "normal" rats receiving SC 14266 was significantly higher than that in those rats treated with vehicle. The results suggest that the mineralocorticoid(s) secreted by the enucleated adrenal has a hypertensogenic property but no effect on the suppression of renin secretion under a high sodium intake and the unilateral nephrectomy.

Production of steroids in vivo by regenerated adrenal glands of hypertensive and normotensive rats.

Adrenal steroid secretion rates of pregnenolone, progesterone, deoxycorticosterone (DOC), 18-hydroxydeoxycorticosterone (18-OHDOC), and corticosterone (B) were measured in vivo under conditions of operative stress in unilaterally adrenalectomized and nephrectomized rats in which the left adrenal gland had been enucleated and the cortical tissue allowed to regenerate for 4-7 weeks. For comparison, rats which were only unilaterally adrenalectomized and nephrectomized (UAN) and sham operated controls were used. All rats received a 1% NaCl solution sweetened with 5% sucrose, instead of drinking water. One half of the adrenal-enucleated rats developed hypertension (ARH) with blood pressures ranging from 150-210 mm Hg, one half remained normotensive (AR), although the kidneys and hearts were enlarged to the same extent in both groups. The hypertrophy of the kidney was less marked in UAN rats than in AR or ARH rats. Control rats which had two adrenal glands secreted about 3 μg pregnenolone and progesterone per 1...

Restoration of adrenal-regeneration hypertension in corticosterone-blocked rats by ACTH.

Adrenal-regeneration hypertension developed uniformly in uninephroadrenalectomized, contralaterally adrenal-enucleated rats, but not in uninephroadrenalectomized controls, maintained on a high salt intake. Adrenal regeneration and the accompanying hypertension were both blocked by daily administration of 1 mg of corticosterone. One unit of ACTH gel given daily had no effect on either the blood pressure or the adrenal weight of rats with uncomplicated adrenal-regeneration hypertension or those in which blood pressure elevation was blocked with corticosterone. There were no significant differences in thymus weight between any of the foregoing groups. The daily administration of 4 units of ACTH permitted only slight enlargement of the adrenals of corticosterone-blocked, adrenal-enucleated rats, or of the hypertrophying adrenals of unilaterally adrenalectomized rats. Hypertension was fully restored to the former, but was not developed in the latter. Both groups displayed a degree of thymus involution. It would appear that full morphologic regeneration is not a prerequisite of adrenal-regeneration hypertension, but that adequate steroidogenesis to support the change can be elicited from an atrophied adrenal gland by adequate ACTH stimulation. The thymolytic effect of ACTH is analyzed for its possible relevance in respect to the secretory profile of adrenosteroids.

Blood pressure response of adrenal-enucleated rats to restricted and irregular feeding patterns and to subsequent ad libitum realimentation.

Summary1. Restricted food intake resulted in smaller increases of blood pressure in intact as well as in adrenal-enucleated (AE) rats when compared with corresponding controls but fed ad libitum. However, AE rats showed a greater increase in blood pressure when compared with intact rats, and this holds particularly for the food-restricted groups. 2. A 10-day realimentation regimen following periods of restricted feeding resulted in greater increases of blood pressure in formerly food-restricted AE rats than in corresponding intact animals. This increase in blood pressure occurred although the AE rats did not ingest more NaCl than the ad libitum-fed AE rats and intact controls. 3. It may be concluded that the regenerating adrenal does not lose its hypertensive potential despite food and thus NaCl restriction.

EFFECT OF AN ALDOSTERONE ANTAGONIST ON ELECTROLYTES AND JUXTAGLOMERULAR GRANULARITY IN ADRENAL REGENERATION HYPERTENSION.

Aldactone (SC-9420, spironolactone), an aldosterone antagonist, prevents the increased blood pressure, increased renal weight and shift of potassium out of skeletal muscle cells which occur with adrenal regeneration after enucleation. It also prevents juxtaglomerular (JG) degranulation due to salt feeding in unilaterally nephrectomized, saline-fed controls, but not in unilaterally nephrectomized, saline-fed, adrenal-enucleated rats. The reason for this difference between enucleated and control rats is unknown. Aldactone prevents atrophy of the zona glomerulosa due to saline feeding in control animals. There is a significant positive linear relationship between log zona glomerulosa width and JG granularity, indicating intervention by Aldactone in the renin-angiotensin- aldosterone mechanism. In control rats Aldactone increases serum potassium, muscle intracellular potassium, and muscle intracellular water without much effect on sodium. (Endocrinology 75: 326,1964)

EFFECT OF CROWDING ON HYPERTENSION AND GROWTH IN RATS BEARING REGENERATING ADRENALS.

Summary1. Uninephrectomized, salt-treated rats bearing regenerating adrenals and grouped 3 to a cage developed significantly higher blood pressure than corresponding rats caged singly. Absence of thymic involution in the grouped, adrenal-enucleated rats lends further support to the thesis that the development of hypertensive disease under these conditions is through the secretion of a steroid other than corticosterone. 2. The enhancement of hypertension by crowding occurred in the face of lower dietary and saline consumption and smaller weight gain than was observed in controls housed singly. Similar, but much less consistent changes occurred in intact grouped rats drinking saline or tap water. 3. These observations support the hypothesis that increased population density augments blood pressure levels attained in rats bearing regenerating adrenal glands.