Effect of ageing and hypertension on endothelial modulation of ouabain-induced contraction and sodium pump activity in the rat aorta.
OBJECTIVE
To investigate the endothelial modulation of the rat thoracic aorta sodium-potassium ATPase activity and its possible alteration by ageing and hypertension.


METHODS
Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) aged 5 weeks, 3, 6, 12 and 18 months were anaesthetized. Their aortae were dissected and divided into cylindrical segments and vasomotor responses obtained in segments with or without endothelium were recorded on a polygraph.


RESULTS
Endothelium removal increased ouabain responses in young (aged 3 and 6 months) WKY rat aortic segments, but reduced those obtained in old (aged 18 months) WKY rat segments and in segments from SHR aged 3, 6 and 12 months. An enhancement of contractions in response to ouabain with age was observed in both strains, but it occurred at earlier ages in vessels from SHR. At ages 3 and 6 months, responses to ouabain were higher in intact vessels from SHR than they were in those from WKY, but were lower in endothelium-denuded vessels. In aortic segments from 6-month-old WKY rats and SHR, ouabain reduced or abolished potassium-induced relaxations in segments with or without endothelium, respectively. In vessels from SHR and WKY rats aged 18 months, ouabain abolished potassium-induced relaxations both in intact and in endothelium-denuded vessels.


CONCLUSIONS
Endothelium of WKY rat aorta might release a factor in response to ouabain that modulates its contraction negatively. Endothelium of SHR and old WKY rat aorta releases a contracting factor that modulates ouabain contractions positively. Thus, the inhibitory effect of endothelium on contractions induced by ouabain might be lost as a consequence both of hypertension and of age, being replaced by an endothelium-dependent contracting factor that facilitates ouabain responses.
Ponte
A
A
Departamento de Farmacologia y Terapéutica, Facultad de Medicina, Universitad Autónoma, Madrid, Spain.
Sánchez-Ferrer
C F
CF
Hernández
C
C
Alonso
M J
MJ
Marín
J
J
D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation
D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D009638:Norepinephrine