Teruhiro Nakada

Effect of antihypertensive therapy on lysine incorporation into vascular protein of the spontaneously hypertensive rat

Young spontaneously hypertensive rats (SHR) were either treated with hydralazine or hexamethonium or splanchnicotomized, so that the development of hypertension was effectively arrested for two weeks. The rate of incorporation of 3H-lysine into non-collagenous proteins in vivo of the heart, aorta and mesenteric arteries was determined in the treated SHR, as well as control SHR and normal Wistar/Kyoto (WK) rats. The lysine incorporation into the non-collagenous protein of mesenteric arteries was increased in 8-week-old SHR as compared with WK rats. Teh elevated lysine incorporation in the SHR was abolished by treatment with hexamethonium or by splanchnicotomy, but was not affected by treatment with hydralazine. It is suggested that sympathetic innervation is important fot the increased synthesis of vascular non-collagenous protein during the early hypertensive phase in the SHR.

Lysine incorporation in vessels of spontaneously hypertensive rats: Effects of adrenergic drugs

Synthesis of vascular proteins was investigated by measurement of the incorporation of 3H-lysine into the protein fractions in arteries in young normotensive or genetically hypertensive rats. The effect of 14 days of antihypertensive therapy with clonidine, propranolol, and phenoxybenzamine was examined. The rate of incorporation of 3H-lysine into the non-collagen protein in internal spermatic and testicular arteries or mesenteric arteries in 8-week old spontaneously hypertensive rats/NIH (SHR/N) and in stroke-prone spontaneously hypertensive rats/NIH (SHR SP/N) was significantly greater than that of Wistar Kyoto rats/NIH (WK/N). S.c. injection of clonidine, 200 μg/kg twice daily decreased the incorporation of tritiated lysine into the non-collagen protein in internal spermatic arteries in each strain and mesenteric arteries in WK/N and SHR SP/N, concomitant with a reduction of development of blood pressure. Similar results were obtained following phenoxybenzamine treatment (3.5 mg/kg s.c. twice daily) and to a lesser extent, following smaller dose of same drug (1 mg/kg s.c. twice daily). Propranolol administration, 3 mg/kg s.c. twice daily, was ineffective in decreasing non-collagen protein synthesis in these small arteries and failed to reduce the blood pressure in any strain. The incorporation rates of tritiated lysine into the collagen and elastin were similar in the examined vessels in each strain treated with saline. Decreased collagen synthesis was observed following clonidine treatment in internal spermatic and testicular arteries in each strain. Other vascular proteins did not change despite the effective antihypertensive treatment. A high incidence of muscular hypertrophy of the media in internal spermatic arteries in SHR/N or SHR SP/N was observed in non-treated and propranolol-treated animals. This hypertrophy was not seen following clonidine or high doses of phenoxybenzamine. These results indicate that increased non-collagen protein synthesis in the small arteries in young genetically hypertensive rats precedes the development of severe hypertensive vascular lesions and may be involved in the pathogenesis of spontaneous hypertension.

Nephropathologic Characteristics of a Woman with Bartter’s Syndrome after Prolonged Treatment with Spironolactone

A study was made of two renal biopsy specimens obtained from a 22-year-old woman with Bartters syndrome, the first to substantiate the diagnosis, the second 2 years later after the treatment with spironolactone. The first renal biopsy revealed remarkable hyperplasia and hypertrophy of the juxtaglomerular apparatus. The numerous proliferating cells were characterized by abundant lysosomal granules and dilated endoplasmic reticulum. The macula densa revealed slight proliferation, with narrow intercellular space. The ultrastructural picture of the second biopsy specimen showed increased lipofuscin-like granules in the juxtaglomerular cells, with epitheloid cells of the macula densa showing degeneration and irregular dilatation of the intercellular spaces. However, the light microscopic finding was compatible with that of the first. These findings suggest that the treatment was inadequate although clinical features or biochemical laboratory data were improved.

Clonidin bei vaskulärer Hypertrophie

Um die Pathogenese der mit vaskularer Hypertrophie assoziierten genetischen Hypertonie zu klaren, wurde in der vorliegenden Studie die Inkorporation von Aminosaure in das vaskulare Protein altersstandardisierter normotensiver Ratten und hypertensiver Ratten, von denen einige eine blutdrucksenkende Behandlung hauptsachlich mit Clonidin erhielten, gemessen.