Mitochondrial mass was determined in the heart and liver of rats submitted to 4,400 m (simulated altitude) for 9 mo and their controls at sea level. This was done 1) by evaluation of isolated mitochondrial protein per gram of tissue, 2) by evaluation of the ratio between cytochrome oxidase activity in tissue homogenate and in isolated mitochondria, and 3) by evaluation of mitochondrial numerical and volume density in fixed tissues analyzed by electron microscopy. An increase in mitochondrial mass and a more homogeneous distribution of mitochondria were found in liver. In cardiac tissue an increase in numerical density of mitochondria accompanied by a slight decrease in their mean volume was observed. Maximal physiological rate of mitochondrial respiration (state 3, active respiration), resting respiration, ADP/O, and acceptor control ratio were determined in the isolated mitochondria. No differences were found in the intrinsic properties of mitochondria. The results suggest that chronic mild hypoxia promotes tissue adaptation by increasing the mitochondrial mass or number in liver and heart, respectively, and improves intracellular O2 diffusion by adopting a more homogeneous intracellular distribution of mitochondria in the liver.

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SUMMARY Lerels and distribution of an angiotenslD-fonning enzyme, active at the physiological pH (isorenin), were determined in the central nervous system of 24 rats treated with 25 mg/kg of deoxycorticosterone (DOC) subcutaneously, twice a week, plus saline to drink during 30 days, and in 14 control animals. Different areas of the brain were excised and homogenized. Renin activity and concentration were determined by incubation of the supernatant of each homogenate at pH 7.2 alone and in the presence of an excess of renin substrate. The angiotensin generated was measured by radioimmunoassay. Concentration of the renin-like enzyme was significantly higher in the posterior hypophysis and in the brain stem of the experimental group; isorenin activity was higher in the hypothalamus, cerebral cortex, cerebellum, and brain stem of the DOC-salttreated rats than in the control rats. Changes in the angiotensin-forming enzyme in the central nervous system of experimental animals, active at physiological pH, suggest that this isoreoin system may play a role in the physiological response to DOC-salt in the rat. The significance of the brain isorenin system in the regulation of blood pressure requires further analysis.

THE co-existence of arterial hypertension and renal lesions has been observed for a long time. This fact has induced many investigators to attempt the production of arterial hypertension by experimental modification of the kidney. The methods used have been numerous and varied, e.g. surgical removal of part of the kidney, ligature of the renal artery or some of its branches, reduction of the calibre of the renal vein, ligature of the ureter, multiple emboli of the kidney, irradiation of the kidney, toxic nephritis, renal compression, etc. References to the principal experiments of this nature can be found in the articles by Braun-Menendez [1932], Goldblatt [1937] and Fasciolo [1938b].In 1927, with Biasotti, experiments were done on partial removal of the kidney, and in 1933 with Braun-Menendez on partial occlusion of the renal vein in the dog, but hypertension so obtained was generally inconstant and transient, therefore the experiments were discontinued. Eventually satisfactory and constant results were obtained using the technique of Goldblatt, Lynch, Hanzal & Sumerville [1934], compressing the renal artery and reducing its calibre by means of an adjustable forceps, which caused renal ischaemia and permanent hypertension with 50-100 mm. Hg rise above the initial blood pressure. The arterial tension generally rose from an initial level of 130-140 to 180-250 mm. Hg; 185 animals thus treated were studied.

Vasodilation by agents such as bradykinin and ATP is dependent on nitric oxide, the endothelium-dependent relaxing factor (EDRF). The release of EDRF results in elevation of cGMP in endothelial and smooth muscle cells (9). The signaling pathway that leads to increases in cGMP is not completely understood. The role of protein kinase C (PKC) in the elevation of cGMP induced by ATP and bradykinin was studied in cultured porcine aortic endothelial cells, by measuring PKC phosphorylation of a substrate and by measuring cGMP levels by radioimmunoassay. Extracellular ATP and bradykinin simultaneously elevated cGMP levels and PKC activity. The PKC inhibitors staurosporine, calphostin C, and Cremophor EL (T. Tamaoki and H. Nakano. Bio/Technology 8: 732–735, 1990; F. K. Zhao, L. F. Chuang, M. Israel, and R. Y. Chuang. Biochem. Biophys. Res. Commun. 159: 1359–1367, 1989) prevented the elevation of cGMP elicited by ATP and reduced that produced by bradykinin. Cremophor did not affect the elevation of cGMP by nitroprusside, an agent that directly increases guanylate cyclase activity (9). The PKC activator phorbol 12-myristate 13-acetate, but not a phorbol ester analog inactive on PKC, also elevated cGMP levels. These results suggest that EDRF agonists elevate cGMP in endothelial cells via PKC stimulation.