Comparison of angiotensin II (Ang II) effects in the internal anal sphincter (IAS) and lower esophageal sphincter smooth muscles.
Studies were performed to compare the actions of Ang II in the internal anal sphincter (IAS) vs. lower esophageal sphincter (LES) smooth muscles in vitro, in opossum and rabbit. Studies also were carried out in isolated smooth muscle cells. In opossum, Ang II produced no discernible effects in the IAS, but did produce a concentration-dependent contraction in the LES. Conversely, in the rabbit, while Ang II caused a modest response in the LES, it caused a significant contraction in the IAS. The contractile responses of Ang II in the opossum LES were mostly resistant to different neurohumoral antagonists but were antagonized by AT1 antagonist losartan. AT2 antagonist PD 123,319, rather than inhibiting, prolonged the contractile action of Ang II. The contractile actions of Ang II in the opossum LES were not modified by the tyrosine kinase inhibitors (genistein and tyrphostin 1 x 10(-6) M) but were partially attenuated by the PKC inhibitor H-7 (1 x 10(-6) M), Ca2+ channel blocker nicardipine (1 x 10(-5) M), Rho kinase inhibitor HA-1077 (1 x 10(-7) M) or p(44/42) MAP kinase inhibitor PD 98059 (5 x 10(-5) M). The combination of HA-1077 and H-7 did not cause an additive attenuation of Ang II responses. Western blot analyses revealed the presence of both AT1 and AT2 receptors. We conclude that Ang lI-induced contraction of sphincteric smooth muscle occurs primarily by the activation of AT1 receptors at the smooth muscle cells and involves multiple pathways, influx of Ca2+, and PKC, Rho kinase and p(44/42) MAP kinase.
Rattan
Satish
S
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. Satish.Rattan@mail.tju.edu
Fan
Ya-Ping
YP
Puri
Rajinder N
RN
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001003:Anal Canal / Q000187:drug effects* / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology; D009893:Opossums; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D013045:Species Specificity; D020032:Tyrphostins / Q000494:pharmacology
D004338:Drug Combinations; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D020032:Tyrphostins; D000804:Angiotensin II; C073402:PD 123319; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009529:Nicardipine; D019833:Genistein; D019808:Losartan; C049347:fasudil; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one