Alterations of vascular prostacyclin and thromboxane A2 in Dahl genetical strain susceptible to salt-induced hypertension

Uehara, Yoshio; Tobian, Louis; Iwai, J.; Ishii, Masao; Sugimoto, Tsuneaki

doi:10.1016/0090-6980(87)90038-4

Cited by 51 publications

(31 citation statements)

References 15 publications

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“…8,9 It should be noted that such an activation of prostanoid formation was absent in prehypertensive SHRs 11,12 or in salt-sensitive Dahl rats fed on a low-salt diet. 8,9 This result suggests that prostanoid synthesis is enhanced as a consequence of high BP and/or underlying hypertensive mechanisms. In addition, the acute COX inhibition by indomethacin increased the vascular resistance in perfused SHRs' hindlimbs.…”

Section: Discussionmentioning

confidence: 99%

“…It seems that the magnitude of the BP response to acute inhibition of NO synthase by N G -nitro-L-arginine methyl ester (L-NAME) injection is preserved in both salt and spontaneous hypertension, 1,4 but NO-dependent vasodilatation is clearly insufficient in compensating for major sympathetic hyperactivity, indicating a relative NO deficiency in rats with these forms of hypertension. 6,7 The synthesis and/or release of vasodilator prostanoids (namely prostacyclin (PGI 2 )) has been found to be increased in the blood vessels of Dahl salt-hypertensive (DS-HS) rats, 8,9 DOCA-salt hypertensive rats and spontaneously hypertensive rats (SHRs), 10,11 but not in prehypertensive SHRs. 11,12 Few attempts have been made to evaluate the contribution of these prostanoids to BP regulation.…”

Section: Introductionmentioning

confidence: 99%

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Vasodilator efficiency of endogenous prostanoids, Ca2+-activated K+ channels and nitric oxide in rats with spontaneous, salt-dependent or NO-deficient hypertension

et al. 2011

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Hypertension is associated with the imbalance of vasoconstrictor and vasodilator systems. Vasodilation is usually evaluated in isolated blood vessels, but except for nitric oxide (NO), relatively little attention is given to the in vivo efficiency of particular vasodilator mechanisms. The aim of our study was to evaluate the contribution of endogenous vasodilator prostanoids, Ca 2+ -activated K + channels and NO to blood pressure (BP) maintenance in rats with three different forms of experimental hypertension. Both principal vasopressor systems (the renin-angiotensin system and the sympathetic nervous system) were blocked by captopril and pentolinium in conscious spontaneously hypertensive rats (SHRs), Dahl salt-hypertensive (DS-HS) rats and rats with NO-deficient hypertension, as well as in their normotensive controls. Thereafter, we monitored BP changes in rats subjected to either a sequential or an isolated blockade of prostanoid synthesis by the non-selective cyclooxygenase inhibitor, indomethacin, of Ca 2+ -activated K + channels by tetraethylammonium and of NO formation by N G -nitro-L-arginine methyl ester. All three forms of experimental hypertension were characterized by augmented sympathetic vasoconstriction. The vasodilatation exerted by endogenous prostanoids and Ca 2+ -activated K + channels was enhanced in all forms of hypertension, almost proportionally to BP elevation. On the contrary, NO-dependent vasodilatation was not enhanced in any form of experimental hypertension, and there was a severe relative NO deficiency in both, SHRs and DS-HS rats. In conclusion, our data suggested that there is a compensatory activation of vasodilator prostanoids and Ca 2+ -activated K + channels in rats with experimental hypertension, whereas NO-dependent vasodilatation is not augmented. Thus, the overall activity of vasodilator systems failed to compensate for augmented sympathetic vasoconstriction in hypertensive animals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vasodilator efficiency of endogenous prostanoids, Ca2+-activated K+ channels and nitric oxide in rats with spontaneous, salt-dependent or NO-deficient hypertension

et al. 2011

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“…The association of hypertension and increased TXB 2 urinary excretion or production (or both) by renal structures was reported first in SHR 1 '*• '• 6 and subsequently in rats with renal ablation hypertension, 7 Dahl salt-sensitive hypertensive rats, 16 and two-kidney, one clip hypertensive rats." Rats with severe hypertension and vascular disease may feature infiltration of the arterial vascular wall by bloodformed elements that are capable of synthesizing TXA 2 .…”

Section: Discussionmentioning

confidence: 99%

Role of pressor prostanoids in rats with angiotensin II-salt-induced hypertension.

Mistry

Nasjletti

1988

Hypertension

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SUMMARY This study was designed to assess the contribution of thromboxane A 2 to high blood pressure in rats with angiotensin II (Ang ID-salt hypertension. Hypertension was induced in rats drinking 0.15 M NaCl by infusion of Ang II (125 ng/min i.p.) for 12 days. Relative to values hi waterdrinking rats without Ang II infusion, Ang II-salt hypertensive rats exhibited augmentation (p < 0.05) of blood pressure (from 129 ± 3 to 217 ± 12 nun Hg), urinary thromboxane B 2 excretion (from 5.4 ± 0.9 to 25.4 ±2.1 ng/day), and thromboxane B 2 release from renal cortex slices (from 71.3 ± 6.7 to 121.1 ± 14.4 pg/mg) and aortic rings (from 28.8 ± 2.9 to 115.8 ± 12.8 pg/mg). Treatment with an inhibitor of thromboxane A 2 synthetase, UK 38485, had no effect on blood pressure hi normotenslve and Ang II-salt hypertensive rats. Treatment with a thromboxane A 2 receptor blocker, SQ 29548, decreased blood pressure in Ang II-salt hypertensive rats from 191 ± 9 to 152 ± 9 mm Hg after 3 hours, but it had no effect on blood pressure hi normotensive rats. Since SQ 29548 interfered with the pressor effects of the prostaglandin endoperoxide analogue U-46619, prostaglandin F^, and 9a, 11/3-prostaglandln F 2 , we suggest that the SQ 29548-induced blood pressure reduction in Ang II-salt hypertensive rats is the manifestation of blockade of the vascular actions of one or more endogenous prostanoids including thromboxane A 2 and prostaglandin endoperoxides. If so, pressor prostanoids may be contributory factors in the pathogenesis of severe Ang II-salt hypertension hi rats. 6 accompany the development of hypertension in spontaneously hypertensive rats (SHR). The development of hypertension in rats with subtotal renal ablation and in saline-drinking rats infused with angiotensin II (Ang II) also is accompanied by increased TXB 2 urinary excretion.7 ' 8 Since thromboxane A 2 (TXAj), the biologically active precursor of TXB 2 , produces vasoconstriction and platelet aggregation, 9 the possibility arises that TXA 2 contributes to the pathogenesis of hypertension and associated vascular and renal disturbances in SHR and in other models of hypertension featuring augmentation of TXA 2 synthesis.Participation of TXA 2 in the mechanisms of hypertension also is suggested by reports that treatment with inhibitors of TXA 2 synthetase lowers blood pressure in SHR1 ' 21011 and in rats with subtotal renal ablation hypertension, 7 in association with improvement of renal hemodynamic and excretory functions and reduction of hypertension-related structural lesions of the renal microvasculature and glomeruli. 2 ' 7 However, in a recent study, blood pressure in SHR was affected by neither a TXA 2 synthesis inhibitor nor a TXA 2 receptor antagonist/ indicating that it is premature to assign to TXA 2 a role in the pathogenesis of hypertension.In saline-drinking rats, chronic infusion of Ang II causes severe hypertension associated with increased urinary excretion and glomerular synthesis of TXB 2 . 8 The present study was designed to assess the contribution of TXA ...

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“…TXA 2 released in the medium was measured in the form of TXB 2 , using a direct radioimmunoassay method previously described. 9 Antiserum was raised in rabbits in our laboratory. Measurements were normalized to the dry tissue weights of aorta.…”

Section: Materials and Methods Experiments 1: Vascular Capacity To Promentioning

confidence: 99%

“…8 In addition, experimental models of genetic hypertension have been shown to possess an enhanced vascular TXA 2 generation. 9 ' l0 Further, prostaglandins exert an influence on the proliferation of various cells," and thromboxane B 2 (TXB2) stimulates the proliferations of cell lines such as 3T3 cells 12 and melanoma cells. 13 Thus, we propose that enhanced vascular TXA 2 generation to some extent participates in the increase in vascular wall thickness in SHR, which may be partly manifested by hyperplasia of VSMCs.…”

Section: S Pontaneously Hypertensive Rats (Shr)mentioning

confidence: 99%

Thromboxane and vascular smooth muscle cell growth in genetically hypertensive rats.

et al. 1988

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SUMMARYThe vascular wall has the capacity to produce thromboxane A 2 . However, the role of vascular thromboxane A 2 is still uncertain. In this study, we examined the relationship between vascular thromboxane A 2 generation and vascular smooth muscle cell growth in spontaneously hypertensive rats (SHR). Vascular thromboxane A 2 generation was significantly enhanced by 49% in 5-week-old and by 117% in 15-week-old SHR as compared with age-matched Wistar-Kyoto rats (WKY). Thromboxane in the prehypertensive stage show hyperplasia or hypertrophy in the cardiovascular system. '-3 Thickening of the vascular wall increases the wall's stiffness and narrows the vascular lumens, thereby producing an elevation of peripheral vascular resistance. Because some humoral substances, such as catecholamines, 4 steroids, 5 platelet-derived growth factor, 6 and insulin, 7 are reported to influence cell proliferation in various cell lines, these factors may be responsible to some extent for the vascular thickness observed in SHR. However, since vascular smooth muscle cells (VSMCs) of SHR From the

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Alterations of vascular prostacyclin and thromboxane A2 in Dahl genetical strain susceptible to salt-induced hypertension

Cited by 51 publications

References 15 publications

Vasodilator efficiency of endogenous prostanoids, Ca2+-activated K+ channels and nitric oxide in rats with spontaneous, salt-dependent or NO-deficient hypertension

Vasodilator efficiency of endogenous prostanoids, Ca2+-activated K+ channels and nitric oxide in rats with spontaneous, salt-dependent or NO-deficient hypertension

Role of pressor prostanoids in rats with angiotensin II-salt-induced hypertension.

Thromboxane and vascular smooth muscle cell growth in genetically hypertensive rats.

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