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P-537: Pioglitazone blunts the blood pressure response to angiotensin II in insulin-resistant zucker rats

Zanchi, Anne ; Perregaux, Christine ; Maillard, Marc ; Nussberger, Juerg ; Brunner, Hans R. ; Burnier, Michel

In: American Journal of Hypertension, 2003, vol. 16, no. S1, p. 232A-232A

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    Titre
    • P-537: Pioglitazone blunts the blood pressure response to angiotensin II in insulin-resistant zucker rats
    Auteur
    • Zanchi, Anne. Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland
    • Perregaux, Christine. Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland
    • Maillard, Marc. Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland
    • Nussberger, Juerg. Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland
    • Brunner, Hans R.. Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland
    • Burnier, Michel. Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • American Journal of Hypertension, 2003, vol. 16, no. S1, p. 232A-232A. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:292336
    Summary
    Thiazolidinediones are high-affinity agonists of peroxisome proliferator-activated receptors (PPAR)-γ which have been found to lower blood pressure (BP) in animal models of diabetes and reno-vascular hypertension. The mechanisms leading to this decrease in blood pressure are still unclear. Since the renin-angiotensin system is a main regulator of blood pressure, we investigated the effects of pioglitazone on blood pressure, plasma renin activity and on the blood pressure response to exogenous angiotensin II in insulin-resistant Zucker rats. Pioglitazone 20mg/kg/d or vehicle were administered for 4 weeks to 8-weeks old fa/fa Zucker rats. Pioglitazone-treated rats were heavier than vehicle-treated rats (respectively 481g±8g vs 437±5g, p=0.0002, mean±SEM) and ate more (35.6±0.5g/d vs 28.9±0.3, p<0.0001). The increase in blood sugar after an intra-venous glucose tolerance test was significantly attenuated in the pioglitazone treated rats at 10,15 and 30 minutes. Systolic (SBP), diastolic (DBP) blood pressure and heart rate (HR) were lower in pioglitazone-treated rats: SBP: 124±3 mmHg vs 144±3, p<0.001; DBP: 80±2 vs 94±2, p<0.001; HR: 369±6 vs 397±8, p<0.01. The BP response to exogenous angiotensin II was significantly attenuated in pioglitazone treated rats. With the 25 ng/kg Ang II dose the increase in BP was 27.8±2.4 mmHg with pioglitazone and 37.5±3.3 with the vehicle (p=0.04) and with the Ang II 100 ng/kg dose the increase in BP was respectively 36.1±2.7 mmHg and 49.2±2.3 (p=0.003). Plasma renin activity was comparable in both groups. In conclusion, these results show that pioglitazone blunts the BP response to angiotensin II in insulin-resistant Zucker rats. This effect may partially explain the blood pressure lowering effect of PPAR-γ agonists