The action of arterial hypertension on lipid and lipoprotein metabolism. I. Salt, adrenal-regeneration and renal (Goldblatt) hypertension.

The purpose of the investigation was to study the alterations in the lipid and lipoprotein content in the blood serum, the liver and the aortic wall of rats with experimentally induced salt, renal (Goldblatt) and adrenal-regeneration hypertension. The experiments were carried out on 59 Wistar rats (25 normotensive controls). It was established that both the serum and the liver lipid patterns vary in the three experimental models of hypertension. Thus, while in salt-induced hypertension no hyperlipidaemia and hyperlipoproteinaemia were established, in renal hypertension the serum lipid and lipoprotein levels were significantly increased in comparison to the controls. The cholesterol content in the liver was increased in all the three models of hypertension. The remaining lipid fractions were within normal ranges or a little decreased in salt-induced hypertension, while in renal and adrenal-regeneration hypertension their quantity was significantly increased. A two weeks' treatment with hypotensive prostaglandin E1 diminished the lipid and lipoprotein contents in the liver of rats with adrenal-regeneration hypertension, only cholesterol remaining unaltered. The blood serum level of free fatty acids increased in all the three models of experimental hypertension, as did the cholesterol and beta-lipoprotein level in the aortic wall. The alterations in lipid and lipoprotein metabolism established in this study are regarded as specific for the hypertensive process itself, since no histological alterations characteristic of atherosclerosis were observed.

The action of arterial hypertension on lipid and lipoprotein metabolism. II. Qualitative and quantitative alterations of blood serum, liver and aortic lipids and lipoproteins in Okamoto-Aoki rats with spontaneous hypertension.

The purpose of the study was to investigate alterations in the content of the basic lipid fractions, and of the low density lipoproteins (LDL) in the liver, the blood serum and aorta, as well as to determine by acrylamide disc electrophoresis the hyperlipoproteinaemic type of spontaneously hypertensive rats (SHR) which are considered as the most suitable model of essential hypertension. The experiments were carried out on 25 normotensive control Wistar rats and 30 SHR (Okamoto-Aoki strain). An augmentation of lipid metabolism in the liver and a moderate hyperlipidaemia mainly due to an increase in triglycerides was found. The quantitative alterations of the lipid fractions corresponded with the qualitative alterations of the lipoproteins, an intensive and permanent pre-beta-LP fraction being established. In all the SHR a peculiar pattern of hyperlipoproteinaemia differing from the basic Fredickson-Lees patterns by a LP-fraction located between tha alpha- and beta-LP fractions was also established. The alterations in the lipid and lipoprotein metabolism in SHR are considered as connected with the hypertensive state itself since no accompanying atherosclerosis was observed.

Plasma renin activity in patients with renovascular hypertension.

Changes of plasma renin activity (PRA) were studied in 45 patients with renovascular hypertension. Peripheral PRA was assayed by Serebovskaya's modification of Pickens' biological method; in 13 patients it was additionally assayed in blood samples taken from both renal veins. In some of the patients who were not surgically treated PRA was followed up over a period of 1 to 5 years. The interrelation between PRA and the sex and age of the patients, the duration and the severity of the disease, the clinical and the morphological type of renovascular hypertension, as well as uni- or bilateral involvement of the renal artery is discussed. PRA was increased during the early stage of renovascular hypertension, while later it became normal. PRA of renal vein blood samples, from the kidney with a constricted renal artery, reflects more exactly the dynamics of the changes in the pressor system of the kidney. The assay of PRA is of special importance in the evaluation of the indications for surgical treatment and of the effect of reconstructive surgery.

Coenzyme alterations in rats with experimental hypertension.

The changes in the content of pyridine nucleotide coenzymes (NAD+ and NADH) in several models of experimentally induced hypertension, differing in mechanism (genetic spontaneous hypertension, renal one kidney Goldblatt hypertension, Adrenal-regeneration hypertension after INGLE-HIGGINS and Skelton, and NaC1 hypertension) were studied. An obvious difference between the changes in NAD+ and NADH in the various models of hypertension, was established: Thus in NaC1 hypertension a high level of the coenzymes in the kidneys and in the vessel wall was found, while the liver coenzyme content was in normal ranges. In ARH the coenzyme level was elevated not only in the kidneys and in the vessel wall, but in the liver as well. Treatment with hypotensive antilipolytic prostaglandin E1 decreased the coenzymes in ARH to normal values. Renal hypertension was characterized by a low content of oxidized NAD, an increased NADH, and a decreased NAD+/NADH ratio in the kidneys and the liver, while in the vessel wall the coenzyme level was moderately increased. The coenzyme changes in the kidneys of SHR were similar to those in renal hypertensive rats. However coenzyme level in the vessel wall of SHR was lower than in all the other forms of hypertension.

Renin activity in the brain, the kidneys and the peripheral plasma or rats with different experimental models of hypertension.

Renin activity (RA) in peripheral plasma, as well as in renal cortex and brain (cortex, stem and medulla) homogenates of rats with spontaneous, Goldblatt, NaCl, adrenal-regeneration and neurogenic hypertension was biologically assayed. The results suggest that RA exists not only in the brain of normotensive but of hypertensive rats as well. RA in the medulla is higher than in other brain areas and in the kidney, both in normotensive and in hypertensive rats with the exception of rats with adrenal regeneration and NaCl hypertension. In most of the experimental forms of hypertension (neurogenic, renal, spontaneous) in which RA in the medulla is increased, the role of the brain renin-angiotensin system seems to predominate, while in forms in which renal RA is elevated (adrenal regeneration) the kidney renin system most probably plays a more important role. A definite inverse interrelation between the brain and the kidney renin-angiotensin systems was established. The interrelation between the two renin systems in NaCl hypertension could not be evaluated, since exogenous factors (Na), which interfere with the kidney renin system, play a considerable role in the pathogenesis of NaCl hypertension.