Modification of the Effects of Hypertension on Lysosomes and Connective Tissue in the Rat Aorta

Abstract

The relationship of lysosomes to the vascular effects of hypertension and the possible modification of these effects by anti-inflammatory agents (methylprednisolone and aspirin), vitamin E, and estrogen were studied. Each of these agents was given to a group of hypertensive rats; untreated hypertensive rats and normotensive rats served as controls. Vessel wall morphology and dimensions of aortas from hypertensive rats were unaffected by treatment. Usual connective tissue accumulations seen in hypertensive vessels were suppressed to normotensive levels in the methylprednisolone-and estrogentreated hypertensive groups. Two lysosomal enzymes, acid phosphatase and Nacetyl-/3-d-glucosaminidase (NAGA), increased over normal levels in hypertensive vessels from 1.03 ± 0.08 (SE) to 2.04 ± 0.19 /imoles/aortic pair hour" 1 and from 1.10 ± 0.24 to 4.57 ± 0.38 /^moles/aortic pair hour" 1 for the respective enzymes. Normal enzyme levels in estrogen-treated hypertensive rats (1.14 ± 0.15 /^moles/aortic pair hour" 1 for acid phosphatase and 2.04 ± 0.44 /imoles/aortic pair hour" 1 for NAGA) and intermediate levels in methylprednisolone-treated hypertensive rats (1.35 ± 0.10 /tmoles/ aortic pair hour" 1 for acid phosphatase and 2.48 ± 0.54 /^moles/aortic pair hour" 1 for NAGA) were found. Other treated groups showed the usual elevations associated with hypertension. These group differences were also seen after cytochemical staining for lysosomal acid phosphatase and NAGA. The parallel changes in aortic connective tissue and lysosomal enzymes in hypertension and their modification by two drugs suggest that these events are related. KEY WORDSiV-acetylglucosaminidase aspirin elastin collagen acid phosphatase estrogen methylprednisolone vitamin E vascular smooth muscle

Effects of hypertension and its reversal on aortic metabolism in the rat.

“…4 In our studies, WKY rats treated with DOC for 7 weeks had increased total amounts of connective tissue proteins, and following an 11-week period when the hypertension was reversed, aortic weights remained greater than controls, as did the total amount of connective tissue proteins. However, activity of the lysosomal enzymes did decrease substantially during the period of reversal.…”

“…21 ' 22 Histochemical studies also localized both enzymatic activities within rat aortic lysosomes. 4 Neither of those studies showed an exclusive localization of either NAGA or acid phosphatase within lysosomes, and it is possible that enzymatic activity also is associated with other cellular fractions. 5'-Nucleotidase activity was shown to be localized in plasma membrane-enriched fractions from rat aorta 14 and would appear to be a reliable marker for that membrane.…”

“…Changes in the vascular endothelium of hypertensive animals may lead to increased vascular permeability and smooth muscle cell proliferation, thereby contributing to the development of atherosclerotic lesions. 1 " 3 Wolinsky et al 4 have VOL. 43, No.…”

Hydrolase activities in the rat aorta. I. Effects of diabetes mellitus and insulin treatment.

“…Rings were rinsed in cacodylate buffer with 7.5% sucrose for 24 hours. For cytochemical studies, sections were incubated for acid phosphatase and N-acetyl-/3-glucosaminidase activities, as previously described, 12 and examined by light microscopy. Unincubated samples and sections incubated for acid phosphatase activity were postfixed in osmium, embedded, and examined by electron microscopy.…”

Aldosterone binding sites in aortic cell cultures from spontaneously hypertensive rats.

“…Physiological evidence derived from rat hypertension models suggests that mineralocorticoids also have a direct effect on the blood vessel wall during the prehypertensive and hypertensive states. These effects include vessel wall hypertrophy 1 and significant increases in cellular ion content and ion turnover. 2 -3 Similar structural and functional changes have been found in various arteries of spontaneously hypertensive rats but not in normotensive control rats.…”