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


CONCLUSIONS
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.
Milei
José
J
Instituto de Investigaciones Cardiológicas Prof. Dr. Alberto C. Taquini, Universidad de Buenos Aires, Argentina.
Cao
Gabriel
G
Grana
Daniel R
DR
Toblli
Jorge E
JE
D000818:Animals; D001794:Blood Pressure; D002344:Carotid Body / Q000378:metabolism* / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005725:Ganglia, Autonomic / Q000378:metabolism* / Q000473:pathology*; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D017395:Plasminogen Activator Inhibitor 1; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1