Hypertension induces compensatory arterial remodeling following arteriotomy.

BACKGROUND

Hypertension has been traditionally considered a risk factor for restenosis following carotid arteriotomy. Genetic and morphological response to carotid arteriotomy in normotensive Wystar-Kyoto (WKY), spontaneously hypertensive (SHR), and Milan hypertensive (MHS) rats were analyzed.

MATERIAL AND METHODS

C-myc, angiotensin II receptor-1 (AT1), angiotensin II receptor-2 (AT2), endothelin-1 receptor A (ET(A)), endothelin-1 receptor B (ET(B)), Bcl-2 family-members (Bcl-2/Bax, Bcl-X(L/S)) were analyzed in surgically injured as well as uninjured carotids of WKY and hypertensive strains (HS). Thirty-day histology and morphometry were accomplished on injured and uninjured carotids.

RESULTS

C-myc mRNA is activated earlier and/or to a greater extent in hypertensive strains than in WKY. AT1 mRNA increases in WKY after injury, while it decreases in SHR and MHS. AT2 shows the opposite, decreasing in WKY and increasing in hypertensive strains. ET(A) mRNA decreases in all strains although with different timing and levels, associated with a replacement by ET(B) mRNA. Bcl-2/Bax ratio gradually decreases in WKY, while it shows only a transient decrease in SHR and MHS 4 h after the injury. Negative remodeling is observed in all injured carotids, although neointima was detected in WKY only. Thirty days following arteriotomy, morphometry demonstrated a significant decrease of luminal area, with consistent gain in the medial area in WKY, whereas hypertensive strains showed significant increase of the luminal area, consistent with a contemporary decrease of the medial area.

CONCLUSIONS

Vaso-relaxant AT2 and ET(B) induced limited vasoconstriction in HS. Less apoptosis in hypertensive rats reduced cell proliferation, contrasting c-myc. These responses favorably modulated media/lumen area ratio following arteriotomy in HS.