Immunological Depression in Spontaneously Hypertensive Rats

Takeichi, Noritoshi; Suzuki, Kazufumi; Okayasu, Takeshi; Kobayashi, Hiroshi

doi:10.1536/ihj.21.590

Cited by 31 publications

(45 citation statements)

References 7 publications

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“…The concept of investigating the role of IL-2 and other immune cell modulators in the pathogenesis of hypertension is of great scientific interest and potential therapeutic usefulness, as previous studies have demonstrated that SHR have depressed T cell function and fewer thymic T cells than normotensive allogeneic strains. 4 -7 A significant reduction in blood pressure has been observed 6 -14 in SHR with established hypertension given Wistar-King-Aptekman or Wistar thymic implants. This attenuation of hypertension obtained by thymic implantation was dependent on multiple implants, and in one study, 6 this attenuation was transient.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-2 does not attenuate hypertension in spontaneously hypertensive rats.

et al. 1990

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It was recently reported that interleukin-2, when administered as a single bolus injection (5,000 units/kg), could prevent the development of hypertension in young spontaneously hypertensive rats and lower blood pressure to normotensive levels in spontaneously hypertensive rats with established hypertension. Consequently, efforts were made to duplicate this finding. Male spontaneously hypertensive rats (35 days old) were injected subcutaneously with 50,000 units/kg (3,500 units/rat) of recombinant interleukin-2 (Amgen) and had systolic blood pressure measured twice weekly by the tail-cuff technique. Systolic blood pressure in the interleukin-2-treated group was not significantly different from the vehicle-treated control group at any time point over 32 days of follow-up. A second injection of recombinant interleukin-2 (5,000 units/kg) was administered 32 days after the first injection. Again, no reduction in blood pressure was observed in the lnterleukin-2-treated group over an additional 38 days. Mean arterial pressure (±SEM) measured via intra-arterial cannula in conscious rats at age 105 days (38 days after the second treatment) was 168.5±3.5 mm Hg in interleukin-2-treated spontaneously hypertensive rats and 1703±3.6 mm Hg in vehicle-treated controls. Both recombinant interleukin-2 preparations conformed to their respective manufacturer's indicated specific activity as determined by the ability of the interleukin-2 to induce proliferation of the interleukln-2-dependent cell line HT-2. Thus, this study demonstrated that interleukin-2 was ineffective in preventing or attenuating hypertension in spontaneously hypertensive rats. (Hypertension 1990;16:468-471)

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Section: Discussionmentioning

confidence: 99%

Interleukin-2 does not attenuate hypertension in spontaneously hypertensive rats.

et al. 1990

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“…40 Additional studies suggested that hypertension in this model was associated with altered immune reactivity, as evidence by impaired blastogenic responses and altered cellular immune reactivity. 41 Our group has hypothesized that the benefit of immunosuppression on salt sensitivity may relate in part to a direct inhibition of the inflammatory response that occurs in the kidneys in SSHTN. Indeed, we have noted a remarkable relationship between the presence of T cells and macrophages in the interstitium with salt-sensitive blood pressure in numerous models.…”

Section: Renal Microvascular Disease and Interstitial Inflammation Armentioning

confidence: 99%

The role of renal microvascular disease and interstitial inflammation in salt-sensitive hypertension

Rodríguez‐Iturbe¹,

Johnson

2010

Hypertens Res

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Primary (essential) hypertension has been shown to be mediated by a relative impairment in sodium excretion by the kidney, but the mechanisms responsible for this defect are still being clarified. Increasing evidence suggests a role for subtle acquired renal injury in mediating this process. Microvascular injury is present in the majority of subjects with hypertension. The development of arteriolosclerosis, primarily of the afferent arteriole, may interfere with glomerular autoregulation, whereas the loss of peritubular capillaries may facilitate local ischemia. These changes favor the localization of T cells and macrophages into the interstitium, which, coupled with local oxidative stress and angiotensin II generation, may contribute to the impaired pressure natriuresis observed with salt-sensitive hypertension. Consistent with this hypothesis, therapies that are aimed at blocking the immune response, including thymectomy, genetic alterations in mice resulting in impaired immune responses, or the use of immunosuppressive agents, can protect against the development of hypertension in experimental models. Preliminary data in humans also suggest that the inhibition of the renal inflammatory response may reduce blood pressure. The present investigations are directed to gain insight in the role of the intrarenal T-cell reactivity and autoimmunity in driving the tubulointerstitial inflammation and its participation in the pathogenesis of salt-sensitive hypertension.

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“…23 Especially in the case of genetic hypertension, it has been suggested that the suppressor thymus-derived (T) lymphocyte dysfunctions and subsequent autoimmunities would bring about vascular injuries and renal damage, both of which are supposed to contribute to the development and maintenance of hypertension. 4 " 6 In fact, it has been demonstrated that the periarterial spaces are infiltrated with inflammatory cells in aged spontaneously hypertensive rats (SHR) and these lesions are resolved by immunosuppressive therapy. 7 Moreover, the arterial damage in salt-induced hypertension could not be produced in nude mice.…”

Section: S Ince White and Grollmanmentioning

confidence: 99%

Antihypertensive effect of interleukin-2 in salt-sensitive Dahl rats.

et al. 1994

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We investigated the effects of interleukin-2, which stimulates the proliferation and maturation of thymus-derived lymphocytes, on hypertension and organ injuries in genetically hypertensive rats. Interleukin-2 (5x10* U/kg body wt) was subcutaneously injected into Dahl salt-sensitive rats fed a 4% NaG diet and spontaneously hypertensive rats once a week for 10 weeks. The effects on blood pressure, cardiovascular hypertrophy, and renal function were evaluated. Interleukin-2 treatment lowered blood pressure in Dahl salt-sensitive rats (162 versus 187 mm Hg, P<.005). This antihypertensive effect was associated with an increase in glomerular filtration rate (589 versus 428 mL/d per 100 g body weight, P<.005) and reduction in cardiac weight (268 versus 305 mg/100 g body weight, P<.05). Interleukin-2 also alleviated the marked glomerular sclerosis in Dahl salt-sensitive rats (glomerular injury score, 151 versus 220; P<.001). In contrast, interleukin-2 did not affect the development of hypertension or organ injuries in spontaneously hypertensive rats. Histologically, glomerular and arterial lesions of the kidney were much less marked in spontaneously hypertensive rats than in Dahl salt-sensitive rats. These data indicate that interleukin-2 ameliorates the development of hypertension and cardiac and renal injuries in Dahl salt-sensitive rats. (Hypertension. 1994^3:68-73.) Key Words • interleukin-2 • glomerular filtration rate • hypertension, sodium-dependent • rats, inbred strains • heart hypertrophy S ince White and Grollman 1 reported the implications of autoimmunity in hypertension after a renal infarct, an increasing amount of evidence has been accumulated suggesting an association between hypertension and immune dysfunction in both humans and experimental hypertensive animals.23 Especially in the case of genetic hypertension, it has been suggested that the suppressor thymus-derived (T) lymphocyte dysfunctions and subsequent autoimmunities would bring about vascular injuries and renal damage, both of which are supposed to contribute to the development and maintenance of hypertension.4 " 6 In fact, it has been demonstrated that the periarterial spaces are infiltrated with inflammatory cells in aged spontaneously hypertensive rats (SHR) and these lesions are resolved by immunosuppressive therapy.7 Moreover, the arterial damage in salt-induced hypertension could not be produced in nude mice. 8 More recently, the antihypertensive effects of cytokines, humoral immunomediators produced by immunocompetent cells, were examined in several studies; however, the results were conflicting.913 This controversy may be derived from the differences in cytokines and hypertensive animal models used in the studies.With regard to hypertensive animal models, most of the earlier studies have been performed using SHR or rat models for secondary hypertension. Little data are available as to the role of the immune system in Dahl salt-sensitive (Dahl S) rats, a genetic model for saltinduced hypertension. It has been reported that Da...

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Immunological Depression in Spontaneously Hypertensive Rats

Cited by 31 publications

References 7 publications

Interleukin-2 does not attenuate hypertension in spontaneously hypertensive rats.

Interleukin-2 does not attenuate hypertension in spontaneously hypertensive rats.

The role of renal microvascular disease and interstitial inflammation in salt-sensitive hypertension

Antihypertensive effect of interleukin-2 in salt-sensitive Dahl rats.

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