Contractions induced by angiotensin I, angiotensin II and bradykinin in isolated smooth muscle from the human detrusor.
In isolated human detrusor preparations angiotensin (At)II 10(-9)-10(-5) M caused concentration-dependent contractions. The contractile effect was immediate, and had an amplitude which at the highest concentration used, 10(-5) M, reached 103 +/- 16% of the mean contraction produced by K+ 124 mM (27.6 +/- 1.4 mN). The AtII effect was completely blocked by saralasin 10(-6) M, but was not affected by pre-treatment of the preparations with captopril or enalaprilate. There was a marked tachyphylaxis to the actions of the peptide. AtI (10(-8)-10(-5) M) also caused contractions which were rapidly developing, and subject to a marked tachyphylaxis. At a concentration of 10(-5) M, the mean amplitude was 66 +/- 9% of the K(+)-induced contraction. The contractions were blocked by saralasin 10(-6) M, but not by captopril or enalaprilate 10(-5) M. In contrast, contractions produced by AtI in rabbit mesenteric arteries were practically abolished by the angiotensin converting enzyme (ACE) inhibitors. The contractions induced by both AtI and AtII were practically abolished after pre-treatment in a nominally calcium-free Krebs solution. However, blockade of L-type calcium channels by nifedipine 10(-6) M reduced the responses to both AtI 10(-6) M (by 38 +/- 4%) and AtII 10(-6) M (by 39 +/- 7%), but never abolished the contractions. Bradykinin (Bk; 3 x 10(-8)-10(-5) M) had a contractile effect in detrusor preparations which varied widely between strips. At a concentration of 3 x 10(-6) M, a maximum was reached amounting to 30 +/- 10% of the K(+)-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Andersson
K E
KE
Department of Clinical Pharmacology, University Hospital of Lund, Sweden.
Hedlund
H
H
Stahl
M
M
D000368:Aged; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D011189:Potassium Chloride; D000803:Angiotensin I; D001920:Bradykinin