We have assessed the effects of stretch or endothelin-1 (ET-1) on atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) secretion and gene expression using a new model of isolated right atria from the rat. This model allows for comparatively long-term in vitro study of adult tissue while retaining the anatomic conformation of the atrium. Stretch and ET-1 resulted in a transient stimulation of ANF and BNP secretion, with an initially larger proportional increase in ANF release. Stretch and ET-1 induced a marked increase in BNP gene expression after 1.5 and 4 h, respectively; the increase in BNP mRNA levels was maintained throughout the 8-h experimental period. Stretch and ET-1 also stimulated c- myc and Egr-1 mRNA levels, two markers of mechanical and receptor-mediated transcriptional activation. The selective response of the BNP gene to stretch and ET-1 and the distinct responses of ANF and BNP secretion indicate that the atrial cardiocytes have the capability to individually regulate the synthesis of its endocrine products. This suggests that each hormone plays a specific role in the response of the heart to hemodynamic or neuroendocrine imbalances.

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We examined the relationship between cardiac hypertrophy, myosin heavy chain (MHC) isoform expression, and production of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) before and after the development of DOCA-salt hypertension. DOCA-salt rats exhibited significant left ventricular hypertrophy at the prehypertensive stage (1 week of treatment), without MHC isoform switch or change in natriuretic peptide gene expression. In the hypertensive stage (5 weeks of treatment), pronounced left ventricular hypertrophy was observed, and this was characterized by an increase in beta-MHC protein, resulting in a switch from 90% alpha-MHC to 51% alpha-MHC and 49% beta-MHC. ANF and BNP mRNA levels and peptide content were significantly increased at this stage. Unexpectedly, the MHC isoform switch was evident in the non-hypertrophied right ventricle to the same degree as in the left ventricle. Natriuretic peptide production was also increased in the right ventricle at 5 weeks of treatment, but to a lesser degree than in the left ventricle. In contrast, in the hypertrophied left atrium there was no MHC isoform switch, while ANF and BNP mRNA levels were augmented. Plasma ANF was significantly increased in the prehypertensive stage; this was accompanied by a partial depletion of atrial ANF stores. Plasma BNP was increased only in the hypertensive stage, reflecting an increase in ventricular BNP synthesis and secretion. These results suggest that 1) cardiac hypertrophy, MHC isoform expression, and stimulation of natriuretic peptide production are processes that may be dissociated from each other; 2) increases in plasma ANF without a concomitant increase in plasma BNP reflect atrial hemodynamic overload, while increases in both ANF and BNP in plasma are associated with ventricular hypertrophy; and 3) there exist differences in the storage, secretion, and processing patterns of ANF and BNP in the atria.

In this work, the localization, density, morphology and ultrastructure of secretory structures in aerial organs of Flourensia campestris (FC) and F. oolepis (FO) (Asteraceae) by means of a combination of light, fluorescence, transmission (TEM) and scanning electron microscopy (SEM) were examined. The possible role of secretory structures in the production and secretion of the phytotoxic sesquiterpene (-)-hamanasic acid A ((-)HAA) in both species was also assessed. Capitate glandular trichomes were found in all reproductive organs of FC and FO, and were being reported for the first time. These glandular trichomes, typically associated to edges and veins, were of the same type as those already described for vegetative organs, and were abundant in involucral bracts and corolla of tubulose and ligulate flowers. Their density in reproductive organs of both species was similar (ca. 30/mm 2 ) and lower than that found in leaves (ca. 100/mm 2 ) and stems (ca. 160/mm 2 in FC, and up to 650/mm 2 in FO). Glandular trichomes in vegetative organs followed a species-* Corresponding authors. M. P. Silva et al. 926specific pattern of distribution. TEM and SEM observations suggest that each species differs in the way in which secretory materials are released to the outside: through cracks or pores in FC, or through a loose cuticle in FO. Similar inspections of the secretory ducts revealed lipophilic vacuoles localized in subepithelial and epithelial cells, in which secretions accumulated before being transferred to the duct. The presence of wall ingrowths in subepithelial cells suggests that granulocrine secretion operates in these species. Secretory ducts varied in density and diameter among the organs in both species, with the combination being maximal in woody stems. (-)HAA was only detected in surface secreted resins of both species, and its concentration (2D-TLC, GC-FID) was intimately associated with the distribution and density of glandular trichomes in each organ (capitula, leaves, and stems with primary or secondary growth). In addition, no (-)HAA was detected internally in the resins collected from secretory ducts. The composition of these resins showed distinctive profiles for FC and FO, and only four from ca. 30 compounds detected (GC/MS) were shared by both species. In addition to the elucidation of ultrastructural traits, distribution and density of secretory structures in aerial organs of FC and FO, present findings suggest a functional role for glandular trichomes in the secretion of the putative phytotoxic allelochemical (-)HAA.

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