Role of bradykinins and nitric oxide in the AT2 receptor-mediated hypotension.
Footshocks increases mean arterial pressure and heart rate. Systemic or intracerebroventricular (IVT) administration of losartan, a specific angiotensin AT1 receptor antagonist, not only inhibited the pressor response to footshocks but resulted in vasodepression. Peripheral or IVT administration of PD 123319, a specific angiotensin AT2 receptor antagonist, did not alter the haemodynamic response to footshocks. However, simultaneous blockade of angiotensin AT1 and AT2 receptors by combined systemic or central administration of losartan and PD 12319, eliminated the vasodepressor response to footshocks unmasked in losartan pretreated rats. Our data suggest that activation of peripheral or brain angiotensin AT2 receptor mediated the vasodepressor response to footshocks in the presence of angiotensin AT1 receptor antagonist. We studied the role of kinins and nitric oxide in the vasodepressor response observed after footshocks. The decrease in mean arterial pressure observed after footshocks in losartan treated rats was blunted by systemic or IVT administration of icatibant (HOE 140) or N(G)-nitro-L-arginine-methyl ester, indicating that peripheral or brain kinins and nitric oxide are involved in the hypotensor response to footshocks during angiotensin AT1 receptor blockade. Our results suggest a role for angiotensin AT2 receptor in the regulation of arterial blood pressure, possibly through the release of vasodilator autacoids such as bradykinins and nitric oxide.
Sosa-Canache
B
B
Clinical Pharmacology Unit, School of Medicine, Universidad Centroccidental Lisandro Alvarado, Venezuela.
Cierco
M
M
Gutierrez
C I
CI
Israel
A
A
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D004333:Drug Administration Routes; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006358:Hot Temperature / Q000009:adverse effects; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D007022:Hypotension / Q000097:blood* / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000502:physiology*; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000097:blood*; D012769:Shock / Q000097:blood / Q000150:complications / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; C073402:PD 123319; D009569:Nitric Oxide; C065679:icatibant; D019808:Losartan; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester