Chronic infusion of low-dose angiotensin II potentiates the adrenergic response in vivo.
OBJECTIVE
The aim of this study was to investigate the role of angiotensin II-induced potentiation of the alpha 1-adrenergic contractile response in the aetiology of low-dose angiotensin II-induced hypertension.


METHODS
Wistar rats (250g) received angiotensin II (120 ng/kg per min) from subcutaneous minipumps for 21 days. The responses of vaso-active properties of second-order mesenteric arteries (200 micron) to potassium, phenylephrine, angiotensin II and acetylcholine were assessed. The acute amplification effects of angiotensin II on the response to phenylephrine were examined.


RESULTS
Angiotensin II induced a progressive hypertension, which reached a plateau after approximately 5 days. The responses to potassium, angiotensin II and acetylcholine were not significantly modified in rats treated chronically with angiotensin II. The major finding of this study is that the response to phenylephrine (1-3 mumol/l) was potentiated (sevenfold at 1.75 mumol/l) after chronic treatment with angiotensin II. In control vessels acute addition of angiotensin II (10(-10) mol/l) produced no contraction but induced potentiation of the phenylephrine response (1-3 mumol/l). No further potentiation of the phenylephrine response was observed in the rats treated chronically with angiotensin II.


CONCLUSIONS
Thus, although the direct contractile responses to potassium and angiotensin II remain unaffected following chronic angiotensin II treatment, the alpha 1-adrenergic contractile response to phenylephrine is significantly potentiated by angiotensin II in this model of hypertension. We suggest that this potentiation contributes to the hypertension observed in response to infusion of low-dose angiotensin II.
Dowell
F J
FJ
Institut National de la Santé, Université Paris VII, France.
Henrion
D
D
Benessiano
J
J
Poitevin
P
P
Levy
B
B
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; D000109:Acetylcholine; D011188:Potassium