Effects of Losartan and Enalapril on Small Artery Structure in Hypertensive Rats

Rizzoni, Damiano; Porteri, Enzo; Piccoli, Alfonso; Castellano, Maurizio; Bettoni, Giorgio; Muiesan, María Lorenza; Pasini, Giancarlo; Guelfi, Daniele; Mulvany, Michael J.; Rosei, Enrico Agabiti

doi:10.1161/01.hyp.32.2.305

Cited by 77 publications

(54 citation statements)

References 43 publications

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“…The following parameters were measured: wall thickness, media thickness, internal diameter, media to lumen ratio. For further details, see Rizzoni et al [12][13][14] and Vecchione et al 15 The functional characteristics of the vessels were then evaluated. The vessels were exposed three times to PSS with equimolar exchange of NaCl for KC1 (KPSS) (2 min, with a 10-min interval) to evaluate their response to potassium, the maximal response usually being observed during the third stimulation.…”

Section: Methodsmentioning

confidence: 99%

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Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats

et al. 2009

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The Milan hypertensive rat strain (MHS) is a genetic strain in which cardiovascular phenotypes seem to be dependent, at least in part, on adducin gene polymorphisms. The aim of our study was to evaluate the structure, contractile responses and endothelium-dependent vasodilation in mesenteric small resistance arteries in 12-week-old MHS, (n¼7), age-matched Milan normotensive rats (MNS, n¼7) and congenic strains in which the DNA segments carrying the a-adducin locus from the MHS have been introgressed into the MNS (MNA, n¼7). Systolic blood pressure (tail cuff) and left ventricular weight to body weight were measured. Mesenteric small arteries were dissected and mounted on a micromyograph; the media:lumen ratio was then calculated. Concentration-response curves to acetylcholine and to norepinephrine (NE) were created. Systolic blood pressure was significantly increased in the MHS and MNA strains compared with the MNS. No significant difference in mesenteric small resistance artery structure was observed among the groups; however, a slightly more elevated media:lumen ratio was observed in MNA compared with the MNS. In contrast, left ventricular weight to body weight was significantly increased and ACH-induced dilatation was significantly impaired in the MHS and in MNA compared with MNS. The concentration-response curve to NE in the MHS showed significantly reduced sensitivity to NE; however, maximum contraction was increased in the MHS vs. the other groups. The MHS presents cardiac (but not vascular) remodeling, endothelial dysfunction and a peculiar contractile response to NE, compared with the other groups. The systolic blood pressure increase and trend to vascular remodeling in MNA support the pathogenic role of a-adducin.

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Section: Methodsmentioning

confidence: 99%

“…Wall tension (active force divided by two times the segment length) and active media stress (wall tension divided by media thickness) were then calculated. [12][13][14] If the vessels produced rhythmic activity, the response was measured from the mean active force for the last 20 s of each period.…”

Section: Methodsmentioning

confidence: 99%

Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats

et al. 2009

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“…29 In SHR, the role of the renin-angiotensin system is well established. 30 A potential role of the endothelin system in the arterial functional and structural changes is, however, less clear. 31 Montagnani et al 32 reported that while there is no difference in ET-1-induced contractions between 5-week-old SHR and Wister Kyoto rats, they noted a marked increase in ET-1-induced contractile responses in 12-week-old SHR.…”

Section: Discussionmentioning

confidence: 99%

Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR

et al. 2017

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Endothelin 1 (ET-1), a potent vasoconstrictor, pro-mitogenic and pro-inflammatory peptide, may promote development of endothelial dysfunction and arterial remodeling. ET-1 can be formed through cleavage of big-ET-1 by endothelin-converting enzyme (ECE) or neutral endopeptidase (NEP). We investigated whether chronic treatment with the novel dual NEP/ECE inhibitor SOL1 improves functional and structural properties of resistance-sized arteries of 32-week-old male spontaneously hypertensive rats (SHR). SHR received a chronic 4-week treatment with SOL1, losartan or hydralazine. We then compared effects of inhibition of NO synthase (NOS) (100 μM L-NAME), blockade of ET A -and ET B -receptors (10 μM bosentan) and stimulation of the endothelium with 0.001-10 μM acetylcholine (ACh) in isolated third-order mesenteric resistance arteries. Losartan and hydralazine significantly lowered blood pressure. Losartan decreased the media-to-lumen ratio of resistance arteries. L-NAME (1) increased arterial contractile responses to K + (5.9-40 mM) in the losartan, SOL1 and vehicle group and (2) increased the sensitivity to phenylephrine (PHE; 0.16-20 μM) in the SOL1 group but not in the losartan, hydralazine and vehicle group. Relaxing responses to ACh in the absence or presence of L-NAME during contractions induced by either 10 μM PHE or 40 mM K + were not altered by any in vivo treatment. Acute treatment with bosentan did, however, significantly improve maximal relaxing responses involving endothelium-derived nitric oxide and -hyperpolarizing factors in the SOL1 group but not in the losartan, hydralazine or vehicle group. Thus, chronic inhibition of NEP/ECE improved basal endothelial function but did not alter blood pressure, resistance artery structure and stimulated endothelium-dependent relaxing responses in 32-week-old SHR.

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“…11 Angiotensin II is thought to have an important role in the pathological alterations in the vascular wall, as is supported by the partial reversal of these alterations by chronic treatment with inhibitors of angiotensin-converting enzyme or antagonists of AT1-receptors. 12,13 Endothelin-1 (ET1), another vasoactive peptide, might also be involved in the arterial structural changes in pathophysiological conditions. Apart from being a potent vasoconstrictor, ET1 is also a potent growth-promoting and proinflammatory agent.…”

Section: Introductionmentioning

confidence: 99%

Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

et al. 2012

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Arteries from young healthy animals respond to chronic changes in blood flow and blood pressure by structural remodeling. We tested whether the ability to respond to decreased ( À90%) or increased ( þ 100%) blood flow is impaired during the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats, a model for an upregulated endothelin-1 system. Mesenteric small arteries (MrA) were exposed to low blood flow (LF) or high blood flow (HF) for 4 or 7 weeks. The bioavailability of vasoactive peptides was modified by chronic treatment of the rats with the dual neutral endopeptidase (NEP)/endothelin-converting enzyme (ECE) inhibitor SOL1. After 3 or 6 weeks of hypertension, the MrA showed hypertrophic arterial remodeling (3 weeks: media cross-sectional area (mCSA): 10 ± 1 Â 10 3 to 17 ± 2 Â 10 3 lm 2 ; 6 weeks: 13 ± 2 Â 10 3 to 24 ± 3 Â 10 3 lm 2 ). After 3, but not 6, weeks of hypertension, the arterial diameter was increased (Ø: 385 ± 13 to 463±14 lm). SOL1 reduced hypertrophy after 3 weeks of hypertension (mCSA: 6 Â 10 3 ±1 Â 10 3 lm 2 ). The diameter of the HF arteries of normotensive rats increased (Ø: 463 ± 22 lm) but no expansion occurred in the HF arteries of hypertensive rats (Ø: 471 ± 16 lm). MrA from SOL1-treated hypertensive rats did show a significant diameter increase (Ø: 419 ± 13 to 475±16 lm). Arteries exposed to LF showed inward remodeling in normotensive and hypertensive rats (mean Ø between 235 and 290 lm), and infiltration of monocyte/macrophages. SOL1 treatment did not affect the arterial diameter of LF arteries but reduced the infiltration of monocyte/macrophages. We show for the first time that flow-induced remodeling is impaired during the development of DOCA-salt hypertension and that this can be prevented by chronic NEP/ECE inhibition.

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Effects of Losartan and Enalapril on Small Artery Structure in Hypertensive Rats

Cited by 77 publications

References 43 publications

Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats

Functional alterations of mesenteric small resistance arteries in Milan hypertensive and normotensive rats

Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR

Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

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