Plasminogen activator inhibitor-1 and transforming growth factor-β1 in carotid glomus and autonomic ganglia from spontaneously hypertensive rats

MILEI J, CAO G, GRANA DR, TOBLLI JE

JOURNAL OF HYPERTENSION

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2004 vol. 22 p. 1351 - 1359

0263-6352

Abstract: BACKGROUND: Baroreflex and chemoreflex mechanisms play an important role in the dynamic adjustments of circulation and ventilation during daily life. Recently, we have observed atrophy and marked fibrosis in carotid glomus (CG) from old patients with carotid atherosclerosis who died following stroke. However, a possible limitation to interpretation of the results in that study was the superposition of arterial hypertension, atherosclerosis and aging in the patients. Taking this into account, spontaneously hypertensive rats (SHR) were used in order to study the CG in an experimental model with only hemodynamic stress. OBJECTIVE: To evaluate whether transforming growth factor-beta 1 (TGF-beta 1) and plasminogen activator inhibitor-1 (PAI-1) were involved in the extracellular matrix expansion in CG and autonomic ganglia (AG) in young, male, adult SHR. METHODS: Male SHR (n = 10) and Wistar-Kyoto (WKY) rats (n = 10) were used. Systolic blood pressure (SBP) was measured monthly up to 8 months of age, when the animals were killed; then, CG and AG were excised and processed for light microscopy and immunohistochemistry (TGF-beta 1, PAI-1 and protein S100). RESULTS: SBP was highly correlated (P < 0.01) with CG fibrosis (r = 0.90), AG fibrosis (r = 0.96) and neuron number (r = -0.97). PAI-1 and TGF-beta 1 in CG and AG were significantly increased (P < 0.01) in SHR. CONCLUSION: Severe damage was observed in CG and AG in SHR, which was, in addition, correlated with SBP. These results suggest that permanent high blood pressure produces remarkable lesions in these structures, even when the animals are not old. In view of the fact that CG and AG are of utmost importance in the genesis of cardiocirculatory reflexes, they might be considered as 'target organs' in arterial hypertension.