Altered contractions to endothelin-1, phenylephrine, potassium chloride and relaxations to acetylcholine at various stages of renal hypertension in the rat
Sav. Raghavan et al., Altered contractions to endothelin-1, phenylephrine, potassium chloride and relaxations to acetylcholine at various stages of renal hypertension in the rat, PHARMAC RES, 43(3), 2001, pp. 225-232
This study is aimed at investigating the contraction and relaxation respons
es in the thoracic and abdominal aortae at various stages of hypertension.
Hypertension in the rats was produced by aortic banding and the responses i
n the abdominal and thoracic aortic rings were studied 2 and 8 weeks after
aortic banding. Contractile responses to phenylephrine (10(-6) M), KCl (80
mM) or to endothelin-1 (10(-12) to 10(-6) M) and the relaxation responses t
o acetylcholine (10(-7) to 10(-5) M) were similar in the thoracic and abdom
inal rings of normotensive rats. The intact thoracic rings from 2 week aort
ic-banded hypertensive rats (ABHR) showed attenuated responses to all the c
ontractile agents used. However, the relaxation to acetylcholine was not al
tered. In the rings from 8 week ABHR, the responses to contractile agents w
ere not significantly altered but the acetylcholine-induced relaxations wer
e significantly attenuated. The endothelial-derived relaxing factors might
act to antagonize the vasoconstrictive responses during the onset of hypert
ension but might be disabled, as the endothelial dysfunction becomes predom
inant after 8 weeks of hyper-tension. The results thus suggest that the con
tractile and relaxant responses are differentially altered during different
stages of hypertension. (C) 2001 Academic Press.