Response of the Rat Aortic Media to Hypertension

Wolinsky, Harvey

doi:10.1161/01.res.26.4.507

Cited by 330 publications

(175 citation statements)

References 32 publications

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“…It is now well established that collagen content is increased in hypertension. 10 ' 11 Using the same morphometric methods as in the present study, we reported a similar increase in collagen content in hypertensive rats. 18 '…”

supporting

confidence: 82%

Effect of a nonhypotensive long-term infusion of ANP on the mechanical and structural properties of the arterial wall in Wistar-Kyoto and spontaneously hypertensive rats.

Grand

Poitevin

Benessiano

et al. 1993

Arterioscler Thromb

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A nonhypotensive dose of atrial natriuretic peptide (ANP) was infused (60 pg/kg body wt per day s.c. by osmotic pump) for 25 days in 16-week-old normotensive Wistar-Kyoto rats (WKYs, TI = 12) and age-matched spontaneously hypertensive rats (SHRs, n = 12). During the infusion period, systolic blood pressure, urinary volume, and cyclic guanosine monophosphate (cGMP) excretion/12 hr were measured once a week in both groups. Then mechanical and morphological properties of the arterial wall and plasma ANP levels were assessed and compared with those from control groups of SHRs («=8) and WKYs (n=8) receiving a saline vehicle. The compliance (CC) of the in situ localized carotid artery was measured for pressures ranging from 25 to 175 mm Hg under control conditions and after "poisoning" of smooth muscle tone by potassium cyanide. After pressure fixation, the medial thickness, elastin and collagen contents, and the size and number of nuclei were measured in the thoracic descending aorta. In WKYs, ANP did not modify either mechanical or structural properties of the arterial wall or biochemical parameters. Conversely, in ANP-treated SHRs, CC was significantly increased compared with untreated SHRs under basal conditions (p<0.03) and after potassium cyanide poisoning (/><0.02). Structural properties were also modified by ANP in SHRs, i.e., medial thickness (129.3±4.1 versus 113.1 ±3.3 jum, p<0.01) and nuclear size (8.81 ±0.28 versus 5.52±0.20 /i.m\p<0.0001) in untreated and treated SHRs, respectively. Furthermore, urinary volume and cGMP content were significantly increased during ANP infusion in treated SHRs (p<0.05). The present results indicate concomitant modifications of mechanical and structural properties of the arterial wall in SHRs chronically treated with low doses of ANP. These long-term effects of ANP could be involved in the remodeling of the arterial wall observed during hypertension and could have beneficial effects on cardiovascular diseases in chronic sustained hyperten- fects such as an increase of diuresis, natriuresis, J. JL urinary excretion of cyclic guanosine monophosphate (cGMP), and glomerular filtration rate and a selective regional relaxation of vascular smooth muscle cells 1 that is partially mediated by the activation of particulate guanylate cyclase via its second messenger, cGMP. The vasorelaxant effects of ANP have been extensively demonstrated in in vitro preparations 2 -4 but not so much in in vivo models. Recent studies have demonstrated that long-term infusion of ANP at low doses reduces blood pressure in several animal models of hypertension, including spontaneously hypertensive rats (SHRs). 5 -8 In this strain, it has been previously shown that the antihypertensive properties were more Received August 13, 1992; revision accepted October 30, 1992. marked when the plasma levels of ANP were modestly but chronically elevated than when they were markedly and acutely increased. 8In SHRs, elevated systemic resistances are associated with an increase in arteriolar and arterial wall thickne...

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supporting

confidence: 82%

Effect of a nonhypotensive long-term infusion of ANP on the mechanical and structural properties of the arterial wall in Wistar-Kyoto and spontaneously hypertensive rats.

Grand

Poitevin

Benessiano

et al. 1993

Arterioscler Thromb

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“…2 Increased vascular collagen is also found in hypertension and probably contributes to the increased arterial stiffness of this condition. 3,4 The production of collagen in the vessel wall is likely regulated by a combination of mechanical forces and soluble growth factors. Of the latter, transforming growth factor-␤ (TGF-␤) is known to stimulate synthesis of collagen in vascular smooth muscle cells (SMCs), 5 whereas interferon-␥, fibroblast growth factor-2, and nitric oxide have been shown to decrease SMC collagen production.…”

mentioning

confidence: 99%

Angiotensin II Stimulates Collagen Synthesis in Human Vascular Smooth Muscle Cells

Ford

Pickering

1999

ATVB

100

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Abstract-Angiotensin II is an established regulator of vascular tone and smooth muscle cell (SMC) growth. However, there are little data about its effect on collagen synthesis by SMCs and none regarding the mechanism of such an effect. We studied the effect of angiotensin II on collagen production by human arterial SMCs, using uptake of [ 3 H]proline into collagenase-digestible proteins, and by ribonuclease protection assay for mRNA encoding the pro␣1 chain of type I collagen, the major collagen in arteries. This revealed a dose-dependent increase in relative collagen synthesis rate and a dose-dependent increase in pro␣1(I) collagen mRNA abundance, with the half-maximal effect at 1.7 nmol/L. Angiotensin II-stimulated collagen expression was associated with a 6-fold increase in transforming growth factor-␤ (TGF-␤) production and was inhibited by a neutralizing antibody to TGF-␤. Both collagen production and TGF-␤ release were inhibited by the AT 1 -specific antagonist, losartan, but not by the AT 2 receptor antagonist, PD123319. To determined if tyrosine phosphorylation was functionally linked to collagen synthesis, we studied the effect of 2 mechanistically distinct inhibitors of tyrosine kinase, genistein, and tyrphostin A25. These inhibitors abrogated angiotensin II-mediated procollagen mRNA expression and angiotensin II-mediated TGF-␤ production, whereas the inactive homolog tyrphostin A1 had no effect. We conclude that angiotensin II stimulates collagen production in human arterial SMCs via the AT 1 receptor and an autocrine loop of TGF-␤, induction of which requires tyrosine phosphorylation.

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“…Hypertension is known to be associated with an increased synthesis of arterial elastin, collagen, and fibronectin. 21 -22 * 28 - 29 Cilazapril might have an effect not only on monocyte macrophages but also on noncellular elements in the intima.…”

mentioning

confidence: 99%

Endothelial dysfunction and subendothelial monocyte macrophages in hypertension. Effect of angiotensin converting enzyme inhibition.

et al. 1991

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Hypertension is associated with an impairment of endothelium-dependent relaxation. The angiotensin converting enzyme inhibitors captopril and cilazapril can prevent this endothelial dysfunction. We recently observed that long-term treatment with cilazapril could also prevent subendothelial infiltration by mononuclear cells in spontaneously hypertensive rats. This prompted us to examine whether, in spontaneously hypertensive rats, endothelial dysfunction and subendothelial infiltration by mononuclear cells are associated. These cells were characterized as monocyte macrophages. Infiltration by monocyte macrophages was quantified by morphometry. Endothelial function was estimated by calculating serotonin ratio (maximal contraction to serotonin on isolated arterial rings with endothelium over maximal contraction on paired rings without endothelium). The regional distribution of endothelial dysfunction and subendothelial monocyte macrophages was similar. Both were maximal in the carotid artery, less in the aorta, and nonexistent in the renal artery. A 2-week treatment with cilazapril decreased both endothelial dysfunction (serotonin ratio decreased by 32%) and the number of subendothelial monocyte macrophages in the aorta, which decreased by 38%. We conclude that in spontaneously hypertensive rats, endothelial dysfunction and subendothelial monocyte macrophage infiltration are associated and that cilazapril can decrease both. The observation that angiotensin converting enzyme inhibitors affect subendothelial accumulation of monocyte macrophages may lead to a better understanding of the mechanism of action of this class of drugs. (Hypertension 1991;18:132-141) E ndothelium-dependent responses are altered in hypertension. Acetylcholine 1 -2 and serotonin 3 can induce endothelium-dependent contractions in spontaneously hypertensive rats (SHR) but not in Wistar-Kyoto (WKY) rats. In dogs, acute hypertension provokes an endothelium-dependent potentiation of the coronary vasoconstrictor response to serotonin. Endothelium-dependent relaxation is impaired in SHR and stroke-prone SHR, 3 -56 but endotheliumindependent relaxation is not.6 -8 Similar endothelial dysfunction has also recently been shown in human hypertension. 910 The endothelial vasoconstrictor substance produced in excess during hypertension is a product of the cyclooxygenase pathway 2 -6 ' 7 -11 and is likely to be a prostaglandin endoperoxide such as prostaglandin H 2 since its action is inhibited by thromboxane/endoperoxide receptor antagonists, but

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Response of the Rat Aortic Media to Hypertension

Cited by 330 publications

References 32 publications

Effect of a nonhypotensive long-term infusion of ANP on the mechanical and structural properties of the arterial wall in Wistar-Kyoto and spontaneously hypertensive rats.

Effect of a nonhypotensive long-term infusion of ANP on the mechanical and structural properties of the arterial wall in Wistar-Kyoto and spontaneously hypertensive rats.

Angiotensin II Stimulates Collagen Synthesis in Human Vascular Smooth Muscle Cells

Endothelial dysfunction and subendothelial monocyte macrophages in hypertension. Effect of angiotensin converting enzyme inhibition.

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