Contractile responses of the human urinary bladder, renal pelvis and renal artery to endothelins and sarafotoxin S6b.
1. Endothelin-1 (ET-1), endothelin-3 (ET-3) and sarafotoxin S6b (SRFTX) produced a concentration-dependent tonic contraction of the human isolated urinary bladder, renal pelvis and renal artery with threshold at nM concentration. 2. In the bladder, the following order of potency was found: ET-1 greater than SRFTX greater than ET-3. In the renal pelvis, all peptides displayed similar affinity but, at high concentrations the maximal response was highest for SRFTX followed by ET-1 and ET-3. In the renal artery ET-1 and SRFTX were about equipotent and equieffective while ET-3 produced only a slight and inconsistent (2 out of 5 cases) vasoconstrictor response. 3. As shown previously for the human bladder muscle, the response to ET-1 in the renal pelvis was nifedipine (1 microM)-resistant while a consistent fraction of the response was blocked by nifedipine in the human renal artery. 4. These findings indicate that peptides of the endothelin family exert a potent contractile effect on various human smooth muscles. Participation of dihydropyridine- and voltage-sensitive calcium channels in the contractile response produced by these peptides may vary from one organ to another.
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
C A
CA
Maggi
S
S
Giuliani
R
R
Patacchini
G
G
Barbanti
D
D
Turini
A
A
Meli
D016232:Endothelins; D006801:Humans; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects; D014757:Viper Venoms / Q000494:pharmacology*
D016232:Endothelins; D010455:Peptides; D014757:Viper Venoms; C057354:sarafotoxins s6; D009543:Nifedipine