Arterial responses to bradykinin after ramipril therapy in experimental hypertension.
Angiotensin-converting enzyme inhibitors have been shown to potentiate relaxations to kinins in several arteries, but the effects of long-term therapy on the responses to bradykinin in normotensive and hypertensive animals remain largely unknown. Therefore, the effects of 12-week-long ramipril therapy (1 mg kg-1 day-1) on responses of mesenteric arterial rings in vitro were studied in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Endothelium-dependent relaxations of noradrenaline-precontracted rings to acetylcholine were similar in normotensive rats and ramipril-treated hypertensive rats and more pronounced than in untreated hypertensive group. Higher concentrations of bradykinin (0.1-1 microM) induced slight contractions in noradrenaline-precontracted endothelium-intact rings of normotensive groups and untreated hypertensive group, whereas no response or a transient relaxation were observed in ramipril-treated hypertensive rats. Interestingly, in ramipril-treated hypertensive rats but not in the other groups, 20-min. pretreatment of arterial rings with ramiprilat unmasked or potentiated the relaxations to bradykinin, and these bradykinin-induced relaxations were effectively inhibited by the B2-kinin receptor antagonist Hoe-140. In conclusion, ramipril treatment clearly improved endothelium-dependent arterial relaxation to acetylcholine, and potentiated of even unmasked the dilatory response mediated via the endothelial B2-kinin receptor in spontaneously hypertensive rats. Since these enhancing effects on arterial relaxation in vitro could not be attributed to reduced breakdown of bradykinin, the present results suggest that long-term angiotensin-converting enzyme inhibition potentiated the actions of kinins at level of B2-kinin receptors.
Hutri-Kähönen
N
N
Department of Pharmacological Sciences, University of Tampere, Finland.
Pörsti
I
I
Wu
X
X
Tolvanen
J P
JP
Sallinen
K
K
Kähönen
M
M
D000109:Acetylcholine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine; D009929:Organ Size / Q000187:drug effects; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D018002:Receptors, Bradykinin; D012701:Serotonin; D017257:Ramipril; D000109:Acetylcholine; D001920:Bradykinin; D009638:Norepinephrine