A locally generated angiotensin system in rat carotid body

Previous studies have shown the existence of functional angiotensin II receptors in rat carotid body, which directly alters the carotid chemoreceptor afferent nerve activity. Moreover, chronic hypoxia could result in an enhanced sensitivity of chemoreceptor afferent activity via an AT(1) receptor-mediated calcium signaling in the carotid body. In the present study, the localization and expression of angiotensinogen, the obligatory component for an intrinsic, angiotensin-generating system, were investigated by in situ hybridization histochemistry, immunohistochemistry, RT-PCR, Western blot and Northern blot analysis. In situ hybridization showed the expression of angiotensinogen within the glomus cells of the carotid body. Double immunostaining of angiotensinogen and tyrosine hydroxylase, an immunohistochemical marker for type I glomus cells, elucidated that angiotensinogen protein was specifically localized to the lobules of type I cells. Consistently, RT-PCR and Western blot analysis confirmed the expression of angiotensinogen mRNA and protein, respectively. On the other hand, renin mRNA was not detected using RT-PCR and Northern blot analysis whereas angiotensin-converting enzyme (ACE) mRNA was detected in the carotid body. These data suggest that a locally generated angiotensin system is operated in the carotid body, which might be linked to a renin-independent biosynthetic pathway. Such an intrinsic, angiotensin-generating system and its local regulation by chronic hypoxia should be important in the modulation of cardiopulmonary adaptation in the hypoxic ventilatory response and the electrolyte as well as water homeostasis. (C) 2002 Elsevier Science B.V. All rights reserved.