Ovariectomy-induced changes in the adrenal cortex of spontaneously hypertensive rats

Many lines of evidence indicate that adrenocortical steroid hormones are involved in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). Twenty-eight days after ovariectomy a notable decrease in the sistolic blood pressure (BP) was found in SHR, along with a marked atrophy of their adrenal cortices. The hypothesis is advanced that the ovariectomy-induced lowering in BP in SHR may be, at least partly, mediated by the suppression of the adrenal secretory activity, due to the lack of circulating estrogens, which are well known to stimulate hypophyseal ACTH release

Different effects of neurotensin and neuromedin-N on the proliferative activity of rat adrenal cortex

Evidence indicates that neurotensin (NT) and neuromedin-N (NMN) exerts an adrenocorticotropic effect in the rat. The present study aimed to investigate whether these neuropeptides are able to stimulate the proliferation of rat adrenocortical cells in vivo and to compare their mode of action. Adrenocortical proliferative activity was assessed by the metaphasearrest technique and metaphases were counted per medulla-containing adrenal section. A bolus administration of NT (3 pglrat) resulted in a significant increase in the number of metaphases in both zona fasciculata and the entire cortex, an effect observed 48 h after the in.jection. The administration of NMN (3 yglrat) induced a notable rise in the number of metaphases in the zona fasciculata and the entire cortex within 12 h, followed by a subsequent drop after 24 h and a return to normal values at 48 h. These findings indicate that NT and NMN enhance rat adrenal growth in vivo acting via different mediators

Proliferation and distribution of adrenocortical cells in the gland of ACTH- or dexamethasone-treated rats

The effects of prolonged (7-day) ACTH and dexamethasone administrations on rat adrenocorticalcell turnover have been investigated by combined stereological and metaphase-arrest techniques. ACTH was found to increase the number of parenchymal cells in each adrenal zone; however, ACTH altered the cell distribution in the cortex, lowering their percentage in the zona glomerulosa (ZG) and zona fasciculata (ZF) and enhancing it in the zona reticularis (ZR). The cell birth-rate was markedly raised by ACTH exclusively in ZG and ZF. Dexamethasone notably decreased the number of ZF and ZR cells, without altering that of ZG cells. Moreover. dexamethasone increased the percentage of parenchymal cells in ZG and ZF, and lowered it in ZR. In the adrenal cortices of dexamethasoneadministered animals, metaphases were virtually absent. These data indicate that ACTH increases the cell birthrate in ZG and possibly ZF, and enhances the centripetal migration of newly-formed cells and their accumulation in ZR. Dexamethasone inhibits both proliferation of adrenocortical cells in the outer cortical layers and their centripetal migration into ZR. Moreover, it appears to cause parenchymal-cell loss in the inner adrenocortical layers

Nonclassic endogenous regulators of angiogenesis

Angiogenesis, the process through which new blood vessels arise from preexisting ones, is regulated by several "classic" factors, among which the most studied are vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). In recent years, investigations showed that, in addition to the classic factors, numerous endogenous peptides play a relevant regulatory role in angiogenesis. Such regulatory peptides, each of which exerts well-known specific biological activities, are present, along with their receptors, in the blood vessels and may take part in the control of the "angiogenic switch." An in vivo and in vitro proangiogenic effect has been demonstrated for erythropoietin, angiotensin II (ANG-II), endothelins (ETs), adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide (PAMP), urotensin-II, leptin, adiponectin, resistin, neuropeptide-Y, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and substance P. There is evidence that the angiogenic action of some of these peptides is at least partly mediated by their stimulating effect on VEGF (ANG-II, ETs, PAMP, resistin, VIP and PACAP) and/or FGF-2 systems (PAMP and leptin). AM raises the expression of VEGF in endothelial cells, but VEGF blockade does not affect the proangiogenic action of AM. Other endogenous peptides have been reported to exert an in vivo and in vitro antiangiogenic action. These include somatostatin and natriuretic peptides, which suppress the VEGF system, and ghrelin, that antagonizes FGF-2 effects. Investigations on "nonclassic" regulators of angiogenesis could open new perspectives in the therapy of diseases coupled to dysregulation of angiogenesis

Effects of the prolonged administration of bradykinin on the rat pituitary-adrenocortical axis

The effects of a prolonged administration of bradykinin (BK) andlor D-Arg, [Hyp3, D - P ~ ~ ~ I - aB K , specific antagonist of BK receptors (BK-A) (daily subcutaneous injections of 4 nmol/rat for 6 days) on the function of the pituitary-adrenocortical axis were investigated. BK did not change plasma aldosterone concentration (PAC), but markedly lowered that of corticosterone (PBC) and consequently induced a compensatory hypersecretion of ACTH by the pituitary gland. BK-A did not apparently affect the function and growth of the adrenal gland, but, when administered together with BK, markedly raised both PAC and PBC, and provoked a significant atrophy of the adrenal gland, probably due to loss of parenchymal cells. Taken together, these rather puzzling findings do not appear to provide clear evidence for the involvement of BK in the physiological regulation of adrenocortical growth and steroidogenic capacity in rats

The role of neuromedin B in the regulation of rat pituitary-adrenocortical function

The effects of a 7-day administration of neuromedin B (NMB) andlor ( ~ ~D-rphe~12,)-b ornbesin, an NMB-receptor antagonist (NMB-A) on the function of pituitary-adrenocortical axis were investigated in the rat. NMB raised the plasma concentration of aldosterone, without affecting that of ACTH or corticosterone; the simultaneous administration of NMB-A prevented the effect of NMB. Neither NMB nor NMB-A treatments induced significant changes in adenohypophysis and adrenal weights, nor in the average volume of zona glomerulosa and zona reticularis cells. NMB-A administration lowered the volume of zona fasciculata cells, an effect annulled by the concomitant NMB administration. Our results suggest that NMB specifically stimulates aldosterone secretion, and that endogenous NMB or NMB-like peptides exert a tonic stimulating action on the growth of zona fasciculata cells

Effects of bombesin on the morphology and

The acute and chronic effects of bornbesin (BM) on the structure and function of rat adrenal cortex were investigated by rnorphornetric and radioirnrnunological techniques. An intraperitoneal bolus injection of 2 yglrat BM rnarkedly raised plasma corticosterone (B) concentration (PBC). The intraperitoneal BM infusion (1 yg/rat.h-l) for 1, 2 or 4 days evoked a notable increase in the nurnber of adrenocortical cells, without inducing apparent changes in either PBC or B output by adrenal quarters. Since proliferation and expression of specialized functions are rnutually exclusive states of cells, our findings suggest that the conspicuous stirnulation of adrenocortical-cell proliferation evoked by BM infusion may be responsible for the apparent lack of effect of this treatrnent on B secretion

Fine ultrastructure of chromaffin granules in rat adrenal medulla indicative of a vesicle-mediated secretory process

none5Observation by transmission electron microscopy, coupled with morphometric analysis and estimation procedure, revealed unique ultrastructural features in 25.94% of noradrenaline (NA)- and 16.85% of adrenaline (A)-containing granules in the rat adrenal medulla. These consisted of evaginations of the granule limiting membrane to form budding structures having different morphology and extension. In 14.8% of NA-granules and 12.0% of A-granules, outpouches were relatively short, looked like small blebs emerging from the granule surface and generally contained electron-dense material. A proportion of 11.2% of NA-granules and 4.9% of A-granules revealed the most striking ultrastructural features. These secretory organelles presented thin, elongated, tail-like or stem-like appendages, which were variably filled by chromaffin substance and terminated with spherical expansions of different electron-density. A cohort of vesicles of variable size (30 to 150 nm in diameter) and content was found either close to them or in the intergranular cytosol. Examination of adrenal medullary cells fixed by osmium-zinc iodide (ZIO) revealed fine electron dense precipitates in chromaffin granules, budding structures as well as cytoplasmic vesicles. This data indicate that a common constituent is revealed by the ZIO histochemical reaction in chromaffin cells. As catecholic compounds are the main tissue target of ZIO complexes, catecholamines are good candidates to be responsible for the observed ZIO reactivity. This study adds further to the hypothesis that release of secretory material from chromaffin granules may be accomplished by a vesiclular transport mechanism typical of piecemeal degranulation.noneCrivellato E; D. GUIDOLIN; Nico B; Nussdorfer GG; Ribatti DCrivellato, E; Guidolin, Diego; Nico, B; Nussdorfer, Gg; Ribatti, D

Chromaffin granules in the rat adrenal medulla release their secretory content in a particulate fashion

none4noneCRIVELLATO E; BELLONI A.S.; NUSDORFER GG; RIBATTI D.Crivellato, E; Belloni, ANNA SANDRA; Nusdorfer, Gastone; Ribatti, D