Short treatments of normotensive and hypertensive rats by angiotensin II and nitric oxide inhibitor induce an increase of noradrenaline sensitivity in isolated vena portae preparations.
The aim of the study was to examine the influence of a short-term treatment of conscious Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) by angiotensin II (ANG II) and by ANG II in combination with either l -NAME, HOE 140 or minoxidil on the mean arterial blood pressure (MABP) and the noradrenaline sensitivity in isolated portal vein preparations. MABP was significantly increased by ANG II treatment and ANG II plus l -NAME. However, it was slightly affected by ANG II in association with HOE 140, and significantly lowered by ANG II plus minoxidil. In control animals noradrenaline increased the frequency and the tone of contractile force. While ANG II enhanced the contractile response to noradrenaline, neither in combination with l -NAME, HOE 140 nor minoxidil prevented such an increase in the response to noradrenaline. In the presence of ergotamine, the contractile response to noradrenaline was completely blocked not only in control animals, but also in animals treated with ANG II alone or in combination with minoxidil. However, ergotamine (3 microm) failed to block completely the contractile response to noradrenaline in vessels from animals treated by ANG II in combination with l -NAME or HOE 140. These data suggest that ANG II causes an increase of noradrenaline sensitivity in the isolated portal vein of rat. l -NAME and HOE 140 unmask a contractile response to noradrenaline in the presence of ergotamine which seems to be mediated not only by alpha-adrenoceptors, but may be compensated by an endothelial relaxation.
Datté
J Y
JY
Department of Pharmacology, Christian-Albrechts-University, Hospitalstrasse 4, Kiel, D-24 105, Germany.
Gohlke
P
P
Pees
C
C
Ziegler
A
A
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004878:Ergotamine / Q000008:administration & dosage / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008914:Minoxidil / Q000008:administration & dosage / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011169:Portal Vein / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D000804:Angiotensin II; D009569:Nitric Oxide; D008914:Minoxidil; C065679:icatibant; D004878:Ergotamine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine