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      Functional Tolerance to α-Adrenergic Receptor Blockade in the Spontaneously Hypertensive Rat Highlights the Multifunctional Role of Vascular Angiotensin II in the Development of Hypertension

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          Treatment of spontaneously hypertensive rats (SHR) with α-adrenoceptor antagonists failed to alter the development of hypertension in this animal model. However, agents such as captopril (CAP) and losartan (LOS) which interfere with the renin-angiotensin system effectively prevented the development of hypertension. When tolerance occurred in the presence of doxazosin (DOX) or phenoxybenzamine, there was an enhanced sensitivity to the blood pressure lowering influence of LOS. In the presence of CAP, at a dose that did not retard the development of blood pressure in the SHR, DOX treatment significantly offset the development of hypertension in this strain. These results suggest that a functional tolerance to agents that interfere with the sympathetic nervous system is mediated by the renin-angiotensin system. Angiotensin-converting enzyme inhibition was associated with a normalization of the enhanced contraction of the mesenteric vascular bed seen in preparations from the SHR and a suppression in the development of the vascular amplifier. The results suggest that the sympathetic nervous system is unable to maintain an elevated blood pressure in the SHR during interference with the functioning of the renin-angiotensin system. Conversely, under conditions of α-adrenoceptor blockade, angiotensin II can maintain an elevated blood pressure in the SHR.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          24 September 2008
          : 32
          : 4
          : 247-253
          aDepartment of Clinical and Experimental Pharmacology, The University of Adelaide, bCSIRO Division of Human Nutrition, Adelaide, Australia
          159099 J Vasc Res 1995;32:247–253
          © 1995 S. Karger AG, Basel

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          Pages: 7
          Research Paper


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