Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile<sup>*</sup>

Page, Roy C.; Benditt, Earl P.

doi:10.1021/bi00856a025

Cited by 69 publications

(12 citation statements)

References 18 publications

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“…It has been known for many years that BAPN dosed parenterally or orally has pro found effects in vivo on the physical and bio chemical stability of newly formed collagen and elastin [10][11][12]. By its action as an irre versible inhibitor of lysyl oxidase [13], BAPN drastically reduces the number of cross-links that can be formed between the lysyl residues of both collagen and elastin.…”

Section: Discussionmentioning

confidence: 99%

Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Franklin¹,

Morris²,

Loveday³

1982

J Vasc Res

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The effects of β-aminopropionitrile (BAPN), an inhibitor of collagen maturation, have been examined in three models of hypertension in rats. It is shown for the first time that BAPN has a rapidly developing antihypertensive action in rats with renal (one kidney-one clip) hypertension. The compound also lowered blood pressure in spontaneously hypertensive rats. In both these experiments although BAPN lowered blood pressure it did not affect the hypertension-induced hypertrophy of the aorta. BAPN suppressed the rise in blood pressure during the developing phase of deoxycorticosterone acetate-salt-induced hypertension and in this model the compound also prevented the accompanying aortic hypertrophy. However, another inhibitor of collagen synthesis and maturation, 3,4-dehydroproline, completely suppressed aortic hypertrophy but failed to prevent the rise in blood pressure in deoxycorticosterone acetate-salt hypertension. It is concluded that: (1) BAPN may have a direct antihypertensive action, and (2) inhibition of aortic hypertrophy alone cannot prevent the rise in blood pressure in the developing phase of deoxycorticosterone acetate-salt hypertension.

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Section: Discussionmentioning

confidence: 99%

Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Franklin¹,

Morris²,

Loveday³

1982

J Vasc Res

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“…The availability of agents that selectively inhibit collagen formation and deposition make it possible to determine whether the increased amounts of collagen also contribute to the maintained hypertension. One of these agents, fl-aminopropionitrile, is a fairly specific inhibitor of lysyl oxidase, the enzyme which catalyzes the oxidative deamination of the e-amino groups of lysine and hydroxylysine in collagen and elastin (3)(4)(5). In the absence of lysyl oxidase activity, the formation of crosslinked collagen is blocked.…”

mentioning

confidence: 99%

Reduction of blood pressure and vascular collagen in hypertensive rats by beta-aminopropionitrile.

Iwatsuki¹,

Cardinale²,

Spector³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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#-Aminopropionitrile, a specific inhibitor of lysyl oxidase preventedthe rise in blood pressure induced by deoxycorticosterone-salt in rats. In addition, after the onset of hypertension, administration of P-aminopropionitrile lowered the blood pressure. Concomitant with the lowering of blood pressure, there was a reduction in the more highly crosslinked form of vascular collagen. These findings would indicate that increases in vascular connective tissue are not only sequelae of hyprtension, but may also contribute to the maintenance of eevated blood pressure. We have previously reported that vascular collagen biosynthesis and deposition is increased in hypertensive rats and that these effects are reversed when blood pressure is lowered by antihypertensive drugs (1, 2). Those findings suggested that the deposition of vascular connective tissue is one of the sequelae of hypertension. The availability of agents that selectively inhibit collagen formation and deposition make it possible to determine whether the increased amounts of collagen also contribute to the maintained hypertension. One of these agents, fl-aminopropionitrile, is a fairly specific inhibitor of lysyl oxidase, the enzyme which catalyzes the oxidative deamination of the e-amino groups of lysine and hydroxylysine in collagen and elastin (3-5). In the absence of lysyl oxidase activity, the formation of crosslinked collagen is blocked. This can be demonstrated by a diminution of insoluble collagen (6).In the present study we have shown that administration of f3-aminopropionitrile to rats receiving deoxycorticosterone-salt markedly diminishes the hypertension produced by the steroid. Rats were killed by decapitation. The entire aorta and the mesenteric artery were excised from each animal and perivascular adipose tissue was carefully removed from them. Each vascular tissue was homogenized in 30 volumes of 0.5 M acetic acid in a ground-glass homogenizer, and the soluble collagen was extracted for 24 hr at 40 (10). The extracts were centrifuged at 11,500 X g for 30 min and the supernatants were dialyzed against 10 mM acetic acid. The precipitates, containing the insoluble collagen, were then lyophilized. After this, the supernatants and precipitates were hydrolyzed in 6 M HCl for 20 hr at 105°. Hydroxyproline was measured by the method of Kivirikko et al. (11). These values yield collagen content when multiplied by 6.98 (12).Tissue sections from each experiment were prepared for histological examination. RESULTSChanges in blood pressure and body weight As shown in Fig. 1, the blood pressures of the rats treated with deoxycorticosterone-salt were markedly increased over those of the controls. Administration of (3-aminopropionitrile to rats treated with deoxycorticosterone-salt largely prevented the increase in blood pressure for 5 weeks. After this time, the blood pressure gradually increased to about 170 mm of Hg by the fifteenth week of treatment. At this point, however, the blood pressure was still much lower than in the rats treated with de-o...

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“…It is probable that the monoamine oxidase is a copper containing enzyme [24,25], Recent biochemical studies on maturation of elastin suggest that the formation of crosslinkages in collagen as well as in elastin is catalyzed by a monoamine oxidase [1,3,6,13,16,18,19,21,23]. The monoamine oxidase in connective tissue, however, has not been studied yet.…”

Section: Discussionmentioning

confidence: 99%

A Clinical Evaluation of Serum Monoamine Oxidase, with Special Reference to Hepatic Fibrosis

Ito¹,

Nakagawa²,

Minakuchi³

et al. 1971

Digestion

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Serum levels of monoamine oxidase (SMO) have been determined in 16 normal adults, in 76 patients with hepatic diseases and in 44 patients with non-hepatic diseases. Elevated enzyme levels were found in patients with cirrhosis and in those with chronic hepatitis or liver cancer associated with moderate or advanced fibrosis. It was also observed that levels of SMO increased gradually with progression of hepatic fibrosis. The increased enzyme concentration could not be ascribed to hepatocellular necrosis or cholestasis. In non-hepatic diseases, elevated levels of SMO were observed in the patients with acromegaly, hyperthyroidism and prooxidase gressive systemic sclerosis, in which biosynthesis and degradation of collagen were considered to be enhanced by overproduction of hormones or by unknown causes. The determination of SMO concentration is useful as a supplemental diagnostic procedure for organ fibrosis, especially for advanced hepatic fibrosis.

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Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile^*

Cited by 69 publications

References 18 publications

Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Reduction of blood pressure and vascular collagen in hypertensive rats by beta-aminopropionitrile.

A Clinical Evaluation of Serum Monoamine Oxidase, with Special Reference to Hepatic Fibrosis

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Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile*

Cited by 69 publications

References 18 publications

Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Effects of Inhibitors of Collagen Maturation on Hypertension in Rats

Reduction of blood pressure and vascular collagen in hypertensive rats by beta-aminopropionitrile.

A Clinical Evaluation of Serum Monoamine Oxidase, with Special Reference to Hepatic Fibrosis

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Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile^*