Renin substrate in rat mesenteric artery

Desjardins-Giasson, Suzanne; Gutkowska, Jolanta; García, Raúl; Genest, Jacques

doi:10.1139/y81-079

Cited by 33 publications

(9 citation statements)

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“…Studies of vascular angiotensinogen and reninlike activity have been unable to exclude plasma as their source (46,47). Re et al (48) and Lilly et al (49) have provided evidence for the synthesis of renin by vascular smooth muscle and endothelial cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat.

Campbell¹,

Habener²

1986

J. Clin. Invest.

463

165

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To define the role of local synthesis of angiotensinogen in tissue angiotensin production, we have quantitated angiotensinogen messenger RNA (mRNA) levels in 17 different tissues of four groups of rats: control rats, nephrectomized rats, rats given dexamethasone, ethynylestradiol, and triiodothyronine, and nephrectomized rats given dexamethasone, ethynylestradiol, and triiodothyronine. Angiotensinogen mRNA was identified in 12 tissues: liver, kidney, brain, spinal cord, aorta, mesentery, atria, lung, adrenal, large intestine, stomach, and spleen. Angiotensinogen mRNA was not identified in pituitary, ventricle, testis, small intestine, or pancreas. When expressed per gram tissue wet weight, angiotensinogen mRNA levels of extrahepatic tissues were <4% of hepatic levels. However, when expressed per milligram total RNA, angiotensinogen mRNA levels of brain, spinal cord, aorta, and mesentery were 2642% of hepatic levels. Regulation of angiotensinogen mRNA levels was tissue specific. This demonstration of a widespread tissue distribution of angiotensinogen mRNA may indicate a similarly widespread distribution of local angiotensin systems that are independent of the circulating renin-angiotensin system.

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Section: Discussionmentioning

confidence: 99%

Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat.

Campbell¹,

Habener²

1986

J. Clin. Invest.

463

165

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“…4 " 6 The presence of this local renin was also suggested by the production of angiotensin I (Ang I) by vessels perfused with tetradecapeptide renin substrate (TOP) 7 -8 and by the increased resistance of isolated muscle preparations when perfused with TDP. 9 -12 As regards angiotensinogen, its local production was suggested by its presence in vascular tissue 13 and by the presence of angiotensinogen mRNA in different tis-- 14 More recently, local production of angiotensinogen has also been demonstrated in isolated perfused beating heart. 15 Although a large body of data has been acquired for the different components of the local RAS in isolated large arteries and in cultured vascular cells, as well as by whole-organ perfusion, very little is known about the characteristics of this system in the microvascular network.…”

Section: Eric Vicaut and Xin Houmentioning

confidence: 99%

Arteriolar constriction and local renin-angiotensin system in rat microcirculation.

Vicaut

Hou

1993

Hypertension

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Lntravital microscopy was used in a preparation of rat cremaster muscle that was isolated from its normal blood supply and externally perfused with a physiological solution, thus allowing exclusion of circulating converting enzyme, renin, and angiotensinogen. The arterioles studied were classified as second-, third-, and fourth-order arterioles with mean diameters of 60.5, 29.9, and 14.8 fim, respectively. Topical administration of 1 nmol/mL angiotensin I or 1 nmol/mL tetradecapeptide renin substrate induced marked vasoconstrictions (i.e., 38.5%, 61.5%, and 90.1% and 25%, 34%, and 88% for second-, third-, and fourth-order arterioles with angiotensin I and tetradecapeptide renin substrate, respectively). The angiotensin converting enzyme inhibitor quinapril significantly inhibited the vasoconstrictions caused by either angiotensin I or tetradecapeptide renin substrate. Almost no vasoconstriction was found when angiotensinogen-rich renin-free plasma containing either 2.45 nmol/mL of angiotensinogen or 1.2 /ig/mL renin was administered. Conversely, these two compounds induced significant constrictions in cremaster muscle preparations in which normal blood perfusion (and thus circulating renin and angiotensinogen) was left in place. We concluded that, in skeletal muscle, 1) the microvascular network is a very effective site of local angiotensin converting enzyme activity and consequently an important target site of angiotensin converting enzyme inhibitors; 2) the effects of tetradecapeptide renin substrate are very different from those of angiotensinogen from plasma and suggest that a large part of the effect of tetradecapeptide renin substrate was due to its nonspecific hydrolysis; and 3) at the microvascular level, circulating renin and angiotensinogen are more effective in inducing arteriolar constriction, in the presence of their substrate or associated enzyme, than local renin and angiotensinogen.

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“…6). It has been reported that the inhibitory action on vascular ACE activity is prolonged by repeated adminis tration of ACE inhibitors (15,23,24). Vascular tissue contains the components necessary to generate A-II locally (15,25,26), and it is known that local vascular formation of A-ll is elevated in SHR (26) and 2K, 1 C-RHR (27).…”

Section: Antihypertensive Action In Shrmentioning

confidence: 99%

Antihypertensive action of a new angiotensin converting enzyme inhibitor, (R)-3-((S)-1-carboxy-5-(4-piperidyl)pentyl)amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid (CV-5975), in various hypertensive models.

Inada¹,

Tanabe²,

Kawazoe

et al. 1988

Jpn.J.Pharmacol

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Abstract-Theantihypertensive activity of a new angiotensin converting enzyme (ACE) inhibitor, CV-5975, (R)-3-[(S)-1 -carboxy-5-(4-piperidyl)pentyl]amino-4 oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid, was examined in nor motensive rats and various hypertensive animal models. In spontaneously hyper tensive rats, CV-5975 (1 to 10 mg/kg, p.o.) had a dose-related, sustained anti hypertensive action, which was more potent and longer than that of enalapril. The potency and duration of action of CV-5975 was intensified when it was administered repeatedly or combined with hydrochlorothiazide. CV-5975 (1 mg/kg, p.o.) inhibited the ACE activity of plasma and tissues; inhibition on the ACE activity of the aorta, kidney, and brain was marked when CV-5975 was administered repeatedly. In 2-kidney, 1 clip hypertensive rats (1 to 10 mg/kg, p.o.) and dogs (0.3 and 1 mg/kg, p.o.), CV-5975 had a marked, sustained antihypertensive action, which was more marked than that of enalapril. In normotensive rats (10 mg/kg), 1 -kidney, 1 clip hypertensive rats (3 and 10 mg/kg), and hyporeninemic DOCA/salt hyper tensive rats (1 to 10 mg/kg/day), CV-5975 administered orally once or repeatedly reduced blood pressure, whereas enalapril did not. These results indicate that CV-5975 is a potent and long-lasting antihypertensive agent, the action of which is mediated primarily by inhibiting ACE activity and partly by some unknown mechanisms.

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Renin substrate in rat mesenteric artery

Cited by 33 publications

References 0 publications

Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat.

Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat.

Arteriolar constriction and local renin-angiotensin system in rat microcirculation.

Antihypertensive action of a new angiotensin converting enzyme inhibitor, (R)-3-((S)-1-carboxy-5-(4-piperidyl)pentyl)amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid (CV-5975), in various hypertensive models.

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