Triamcinolone acetonide, triamcinolone hexacetonide, and a combination of betamethasone phosphate and acetate were given intra-articularly in different doses. Plasma levels of the steroids were measured and pharmacokinetic parameters were calculated. As a pharmacodynamic parameter for systemic steroid activity, plasma hydrocortisone levels were monitored for 3 weeks. Results indicate complete absorption from the site of injection over a period of 2 to 3 weeks. Because of its lower solubility, triamcinolone hexacetonide is absorbed slower than triamcinolone acetonide, thus maintaining synovial levels for a longer time and creating lower systemic corticoid levels. Endogenous hydrocortisone suppression correlated with exogenous steroid levels. Threshold concentrations for maximum suppression were determined.

There is a large body of evidence that points to a systemic link between the somatotropic axis and sex hormones, but epidemiologic data on the interactions between the two hormonal systems are still missing. We examined here the associations between the plasma levels of insulin-like growth factor (IGF) I, IGF-II, IGF-binding protein 3 (IGFBP-3), and sex hormones in a population-based sample of 486 men and women, aged 50-80 yr. The strongest association was an age-independent inverse correlation between all three circulating IGF components and sex hormone-binding globulin (SHBG), the major testosterone-binding protein in plasma. Consistent with this, bio-available (non-SHBG-bound) but not total testosterone levels were positively associated with the IGF system in men, and 3 alpha-androstanediol glucuronide was positively correlated with circulating IGFs in women. Moreover, part of the correlation between the circulating IGF system and bone mineral density at the femur and the calcaneus could be accounted for by SHBG. Our data suggest that sex hormones and the GH/IGF system are significantly interrelated in the elderly population. These hormonal interactions may play an important role in human aging and the pathogenesis of age-related diseases.

During the onset of malignant hypertension (MH) in rats treated with deoxycorticosterone trimethylacetate (DOC), plasma arginine vasopressin (AVP) concentrations increase tenfold as a consequence of hypovolemia and hyperosmolality. In benign hypertensive (BH) rats, plasma AVP is increased threefold in comparison with control animals. Plasma renin is markedly suppressed in both BH and MH animals. In MH rats, biologically active AVP antiserum lowers blood pressure (BP) transiently to normal or subnormal levels; in BH rats, a small BP-lowering effect of the AVP antiserum is seen. (Biologically active angiotensin II antiserum does not lower BP in MH rats.) The relationship between the height of BP and plasma AVP concentration in DOC hypertensive rats indicates, when compared with that relationship in diabetes insipidus rats infused with AVP, a marked enhancement of the vasopressor effect of AVP. These findings and the earlier observation of vasopressin-induced vascular damage by Byrom (F. B. Byrom, The Hypertensive Vascular Crisis. London: Heinemann, 1969) strongly suggest that ADH is involved as a vasopressor hormone in the pathogenesis of malignant DOC hypertension.

The administration of corticosterone for 5 consecutive days to normal rats on a standard sodium intake induced negative sodium and water balance. These effects were opposite those observed under DOCA treatment. However, not only under DOCA but also under corticosterone treatment extracellular fluid volume (ECFV) and plasma volume (PV) increased, and blood pressure (BP) rose in parallel. Plasma renin and angiotensin II concentrations declined under the influence of both steroids. Plasma arginine vasopressin concentrations increased under DOCA, whereas they transiently decreased under corticosterone administration. These data suggest that the common mediator for BP elevation due to steroid excess would be an increase in ECFV and PV. The pathways by which this increase is achieved seem to be different. Under DOCA treatment ECFV and PV increased subsequent to renal sodium and water retention. Under corticosterone, however, sodium and water were shifted from intra- to extracellular compartments, and a fraction of this shifted sodium and water was conserved in extracellular space, most likely because corticosterone also affected renal sodium handling.

The data suggest that tetrahydroaldosterone is the most reliable screening test for PA. Tetrahydroaldosterone determination in combination with aldosterone-18-glucuronide and free aldosterone increases diagnostic specificity for PA. Potassium, renin, plasma aldosterone, and basal PARR are inadequate screening procedures because they are subject to high rates of false-positive and false-negative results.

In rats with unilateral renal artery stenosis and an intact contralateral kidney, a malignant course of hypertension (MH) may develop, which is characterized by 1) high BP levels, 2) sodium and water loss and a polyuric-polydipsic syndrome, 3) marked activation of the renin-angiotensin system, 4) malignant nephrosclerosis in the contralateral kidney and high plasma urea concentrations, and 5) deterioration of the animals' general condition. (Some rats exhibit signs of a cerebral vascular crisis; some rats die). When such rats are offered in addition to water 0.9% NaCl, they compulsively drink the saline, BP falls for some days to levels found in the other hypertensive animals, and signs of MH nearly or completely disappear. It is concluded that high saline intake has, for a limited period, a beneficial effect on the malignant course of renal hypertension in rats. The observations made are consistent with the hypothesis that salt and water loss, which ensue subsequent to an increase of BP into a critical high range might trigger the onset of malignant hypertension.

No abstract

Male Sprague-Dawley rats with unilateral renal artery stenosis and a contralateral untouched kidney develop a malignant hypertension (MH) which is characterized by high blood pressures, sodium and water depletion, and subsequent activation of the renin-angiotensin system. In the present studies we found plasma arginine vasopressin (AVP) concentrations-3-fold higher than those in rats with benign renal hypertension, and 4- to 5-fold higher than those in normotensive control rats. Analysis of individual values showed considerable scatter; about 50% of the values fell in the range of benign hypertensive or control rats. When a specific AVP antiserum was injected, iv, into eight conscious unrestrained MH rats, BP transiently fell toward control values in four; in one, BP fell by only 10 mm Hg, and three other MH rats showed no response. In the same rats, injection of a specific angiotensin II antiserum always induced a transient fall in BP. On the basis of these and previously reported observations, we conclude that, subsequent to sodium and water loss and activation of the renin-angiotensin system, vasopressin release is stimulated in a significant number of MH rats and that, in these rats, vasopressin may cause significant systemic vasoconstriction. Thereby vasopressin may contribute to the development of malignant renal hypertension in rats.