Endothelial AT1-mediated release of nitric oxide decreases angiotensin II contractions in rat carotid artery.
The purpose of this study was to examine whether angiotensin II (Ang II) stimulates the release of endothelium-derived nitric oxide, which then impairs the contractions of vascular smooth muscle caused by the peptide, and to determine the receptor subtypes mediating these responses. Experiments were performed on isolated rings of rat carotid artery either incubated in the presence of phosphodiesterase inhibitor for the measurement of intracellular levels of cGMP or suspended in organ chambers for recording of changes in isometric force. Ang II (10(-7) mol/L) caused a twofold increase in intracellular cGMP level in preparations with but not in those without endothelium. The presence of endothelium impaired the contractions evoked by the peptide and caused approximately 50% inhibition of the maximal response to Ang II (3 x 10(-8) mol/L); pD2 values for Ang II were 8.9 +/- 0.1 and 9.6 +/- 0.2 in rings with and without endothelium, respectively. In rings with endothelium the contractions to Ang II were augmented by nitro-L-arginine (an inhibitor to nitric oxide synthase) but not indomethacin (an inhibitor of cyclooxygenase), to reach a response comparable to that of preparations without endothelium. In rings without endothelium losartan (a preferential angiotensin type 1 receptor antagonist) displayed competitive antagonism toward Ang II (pA2 = 9.5); PD 123319 (a preferential angiotensin type 2 receptor antagonist; up to 10(-7) mol/L) did not affect the response to the peptide. Losartan (3 x 10(-9) mol/L) but not PD 123319 (10(-7) mol/L) impaired the endothelium-dependent component of the response to the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Boulanger
C M
CM
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Tex, USA.
Caputo
L
L
Lévy
B I
BI
D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D002339:Carotid Arteries / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D009569:Nitric Oxide; D006152:Cyclic GMP