Vascular angiotensin II receptors in renal and DOCA-salt hypertensive rats.

Schiffrin, E. L.; Thomé, Fernando Saldanha; Genest, Jacques

doi:10.1161/01.hyp.5.6_pt_3.v16

Cited by 44 publications

(23 citation statements)

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“…InsPs in DOCA-salt hypertensive rats responded significantly less than in controls when tissues were challenged during a long period (30 minutes) with 100 nmol/1 ET-1. The responses of thoracic aorta and mesenteric arteries had the same pattern, showing that alterations were similar in large conduit arteries and in resistance arteries, in agreement with our previous results demonstrating blunted vascular responses to ET-1 in conduit arteries such as aortic and mesenteric artery rings 3 and in mesenteric resistance arteries 2 ' of DOCA-salt hypertensive rats. The data of InsP accumulation on long-term stimulation agree with previous findings we have reported 3 but is in contrast to increased responsiveness of InsP to ET-1 shown in another study, 5 which may relate to duration of hypertension.…”

Section: Production Of Diacylgtycerol In Aortasupporting

confidence: 91%

Calcium, phosphoinositide, and 1,2-diacylglycerol responses of blood vessels of deoxycorticosterone acetate-salt hypertensive rats to endothelin-1.

Flückiger

Nguyen

et al. 1992

Hypertension

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In previous studies a decreased responsiveness to endothelin-1 (ET-1) of conduit arteries and resistance vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats was found in comparison with uninephrectomized controls. Decreased isometric force, number of receptors, and inositol phosphate accumulation were reported in the DOCA-salt animals. In the present study effects of ET-1 on cytosolic free calcium, inositol phosphates, and 1,2-diacylglycerol were investigated in blood vessels of DOCA-salt hypertensive rats. Basal cytosolic free calcium, measured with the fluorescent dye fura-2, was 201 ±41 nmol/l in mesenteric arteries of DOCA-salt rats and 45±9 nmol/l in uninephrectomized controls (p<0.01). The maximal response of cytosolic free calcium (to 30 nmol/l ET-1) was 176±22% of the basal value for DOCA-salt and 242±6% for uninephrectomized rats (p<0.05). The concentration giving 50% of the maximum response was 9.0 and 6.5 nmol/l for DOCA-salt rats and controls, respectively. Inositol phosphate production after stimulation with 100 nmol/l ET-1 in the presence of LiCl was lower by at least 30% (p<0.01) in both aorta and mesenteric arteries of DOCA-salt hypertensive versus control rats. Basal levels of diacylglycerol in aorta were similar in DOCA-salt rats and in controls and did not respond to a 100 nmol/l ET-1 stimulation in the DOCA-salt rats, in contrast to the increase found in the control uninephrectomized rats (p<0.05). Thus, the diminished response to ET-1 of DOCA-salt rat arteries may be due to a lower density of ET-1 receptors, resulting in a blunted signal transduction, as reflected by decreased responses of inositol phosphate, cytosolic free calcium, and diacylglycerol. 6 Although endothelin infusion may raise blood pressure, its role in hypertension is unproven. 7 The vascular effects of this peptide have been extensively investigated: endothelins most likely act as paracrine hormones and exert their cellular effects through the phosphoinositide pathway, In a previous study we reported that the density of mesenteric artery ET-1 receptors and vascular responses to ET-1 are decreased in DOCA-salt hypertensive rats.3 Moreover, we demonstrated that vascular accumulation of inositol phosphates (InsPs) in response to ET-1 was significantly lower in DOCA-salt hypertensive rats when compared with uninephrectomized controls. These observations led to the question of whether diacylglycerol (DG) production and intracellular calcium metabolism are also altered in DOCA-salt hypertensive rats. It is indeed well established that DG can be produced by phosphatidylcholine breakdown as well as through the phosphatidyl inositol pathway.10 Therefore, DG levels might not change in parallel with endothelinstimulated InsP production in vascular smooth muscle cells. ET-1 has also been shown to exert a wide range of effects on calcium metabolism: low ET-1 concentrations (<1 nmol/l) provoke calcium influx through calcium channels, 81112 whereas higher concentrations stimulate inositol 1,4,5-trisphosphate-dependent ca...

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Section: Production Of Diacylgtycerol In Aortasupporting

confidence: 91%

Calcium, phosphoinositide, and 1,2-diacylglycerol responses of blood vessels of deoxycorticosterone acetate-salt hypertensive rats to endothelin-1.

Flückiger

Nguyen

et al. 1992

Hypertension

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“…31 In the present study there were no differences in pulse pressure between both groups of patients. Other factors that may be involved in vascular hypertrophy and remodeling in hypertension include the sympathetic nervous system 32 and growth factors such as transforming growth factor-/31, basic fibroblast growth factor, and platelet-derived growth factor 23 as well as other agents and cytokines. Mechanical factors such as decreased compliance 33 also may play a role in remodeling of blood vessels in hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…23 Plasma catecholamines were measured by a radioenzymatic method. 24 Serum sodium, potassium, and creatinine were measured by automated methods.…”

Section: Biochemical Methodsmentioning

confidence: 99%

Effects of a beta-blocker or a converting enzyme inhibitor on resistance arteries in essential hypertension.

1994

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Seventeen male untreated mild essential hypertensive patients aged 41 ±2 years agreed to participate in a double-blind randomized trial to test the effects of antihypertensive treatment on the structure and function of subcutaneous resistance arteries. Patients were treated with either 50 to 100 mg/d atenolol or 2.5 to 5 mg/d cilazapril. Blood pressure before treatment was 148±6/99±1 and 147±2/99±1 mm Hg, respectively. At 1 year of treatment blood pressure was 131±4/85±2 and 132±2/87±1 mm Hg, respectively. Resistance arteries (200 to 400 /xm lumen diameter) dissected from subcutaneous gluteal biopsies obtained before treatment and at 1 year showed that the media-lumen ratio of arteries from patients treated with cilazapril was reduced to 6.31±0.21% from 7.54±0.31% before treatment (/><.05), still slightly but significantly larger (P<.05) than the media-lumen ratio of resistance arteries of normotensive control subjects (5.15±0.30%). In contrast, in arteries from patients treated with atenolol there was no significant change with treatment (7.97±0.60% before and 8.07±0.45% after 1 year of treatment). Active wall tension responses to endothelin-1 were blunted in hypertensive patients and normalized in the cilazapril-treated patients. Depressed active media stress responses to norepinephrine, arginine vasopressin, and endothelin-1 were accordingly normalized in the patients receiving cilazapril as the media width became thinner but were unchanged in those taking atenolol. These results suggest that treatment for 1 year with the converting enzyme inhibitor cilazapril corrects in part the structural and functional abnormalities present in subcutaneous resistance arteries of patients with mild essential hypertension. {Hypertension. 1994^3:83-91.)Key Words • angiotensin converting enzyme inhibitors • adrenergic beta receptor blockers • hypertrophy • blood vessels • hypertension, essential N ormalization of elevated blood pressure in hypertensive patients has been clearly shown to improve survival and decrease the incidence of stroke and renal and heart failure. 15 However, most clinical trials of antihypertensive treatment have failed to show significant beneficial effects on myocardial ischemia, although meta-analyses have indeed allowed benefit to be demonstrated, albeit to a lesser degree than on the incidence of stroke. 67 The reasons for this relative lack of success have been a matter of discussion but remain unclear. One possible explanation could be that altered vascular structure in hypertensive patients is not normalized by antihypertensive treatment. Persistent abnormalities in blood vessels, particularly in coronary arteries and arterioles, may play a role in this outcome.Alteration of large blood vessels in hypertensive patients has been clearly documented and is mainly associated with atherosclerosis.8 However, the increased peripheral resistance that characterizes high blood pressure in animals and humans is above all the consequence of alterations in the smaller arteries and arterioles, called...

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“…7 Plasma renin activity was measured by RIA of angiotensin I produced after a 2-hour incubation of plasma at 37°C and pH 6.5, as previously described. 14 …”

Section: Measurement Of Plasma Immunoreactive Endothelin-1 and Plasmamentioning

confidence: 99%

Increased endothelin-1 content in blood vessels of deoxycorticosterone acetate-salt hypertensive but not in spontaneously hypertensive rats.

1993

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Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced in the endothelium of blood vessels that may play an important role in the control of local blood flow and could be involved in the pathogenesis of hypertension. We investigated immunoreactive ET-1 (ir-ET-1) levels in acid extracts from blood vessels of deoxycorticosterone acetate (DOCA)-salt and spontaneously hypertensive rats. We found that segments of thoracic aorta and the mesenteric vascular bed contain significantly more ir-ET-1 (11.84±0.84 and 17.30±1.89 fmol, respectively) than uninephrectomized control rats (1.78±0.20 and 9.19+0.63 fmol, respectively; p<0.001). High performance liquid chromatography showed that ir-ET-1 of blood vessels of DOCA-salt hypertensive rats eluted in the same position as synthetic ET-1. Significantly increased ir-ET-1 was localized by immunohistochemistry in endothelial cells of aorta and large and small mesenteric arteries of DOCA-salt hypertensive rats. In contrast to the latter, in spontaneously hypertensive rats, vascular content of ir-ET-1 was similar to that of blood vessels of Wistar-Kyoto control rats, at both 6 and 16 weeks of age. High levels of vascular ET-1 may explain the downregulation of vascular endothelin receptors previously described in DOCA-salt hypertensive rats. Furthermore, this suggests that ET-1 may be involved in the maintenance of high blood pressure in mineralocorticoid hypertension. ET-1 is a 21-amino acid peptide produced primarily in endothelial cells' but also in vascular smooth muscle cells.3 Locally produced ET-1 exerts its effects in an autocrine and paracrine fashion to constrict blood vessels by acting on smooth muscle. Through its effect on endothelial cells, it induces the production of endothelium-derived relaxing factor and prostacyclin, which relax underlying smooth muscle cells. 4 The balance between these responses may contribute to the control of blood pressure. 5 The role of ET-1 in hypertension, however, remains unclear. Plasma ET-1 levels in different models of hypertension in the rat and in essential hypertension in humans have been found to be similar or slightly higher in comparison to normotensive controls.6 -9 Recently, we have shown that arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive

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Vascular angiotensin II receptors in renal and DOCA-salt hypertensive rats.

Cited by 44 publications

References 30 publications

Calcium, phosphoinositide, and 1,2-diacylglycerol responses of blood vessels of deoxycorticosterone acetate-salt hypertensive rats to endothelin-1.

Calcium, phosphoinositide, and 1,2-diacylglycerol responses of blood vessels of deoxycorticosterone acetate-salt hypertensive rats to endothelin-1.

Effects of a beta-blocker or a converting enzyme inhibitor on resistance arteries in essential hypertension.

Increased endothelin-1 content in blood vessels of deoxycorticosterone acetate-salt hypertensive but not in spontaneously hypertensive rats.

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