Different responses to angiotensin-(1-7) in young, aged and diabetic rabbit corpus cavernosum.
We evaluated the ability of angiotensin-(1-7) [Ang-(1-7)] to produce relaxation of the corpus cavernosum of New Zealand White rabbits. The reactivity of corpus cavernosal strips isolated from young rabbits (8-10 months old) was assessed in organ-bath chambers. Cumulative concentration response curves for Ang-(1-7), angiotensin II (Ang II), carbachol and sodium nitroprusside (SNP) were established. Ang-(1-7) (10(-12) to 10(-5)M) produced a concentration-dependent relaxation of the corpus cavernosal strips with a pD(2) value of 9.8+/-0.3. Ang-(1-7)-induced maximal relaxant response was reduced by 48+/-2%, 57+/-3% and 76+/-2% in the presence of A-779 (10(-6)M), a selective Ang-(1-7) receptor (AT(1-7)) antagonist, nitro-l-arginine methyl ester (l-NAME) (10(-4)M), an inhibitor of nitric oxide (NO) synthase, or iberiotoxin (5 x 10(-8)M), an inhibitor of calcium-activated potassium (BK) channels, respectively. In contrast, Ang II-induced contraction was increased in the presence of A-779. Carbachol-, SNP- and Ang-(1-7)-induced relaxations were significantly reduced whereas Ang-II induced contraction was significantly increased in the cavernosum strips from older (18-24 months old) and diabetic rabbits compared to the young. Pre-incubation of the cavernosum strips obtained from young, older or diabetic rabbits with Ang-(1-7) resulted in a significant attenuation of Ang II-induced contraction. In conclusion, these results demonstrate that Ang-(1-7) can produce nitric oxide-dependent relaxation of the corpus cavernosum through activation of AT(1-7) and BK channels. Older and diabetic animals showed impaired Ang-(1-7)-mediated relaxation suggesting that aging and diabetes related erectile dysfunction (ED) may be partly due to decreased Ang-(1-7)-mediated relaxation of the corpus cavernosum. Acute pre-incubation with Ang-(1-7) was effective in attenuating Ang II-induced contraction of rabbit corpus cavernosum suggesting that the possible role of Ang-(1-7) in treatment of ED should be investigated.
Yousif
Mariam H M
MH
Department of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
Kehinde
Elijah O
EO
Benter
Ibrahim F
IF
D000375:Aging / Q000378:metabolism*; D000803:Angiotensin I / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007172:Erectile Dysfunction / Q000378:metabolism* / Q000503:physiopathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014665:Vasodilator Agents / Q000378:metabolism* / Q000494:pharmacology
C092006:7-Ala-angiotensin (1-7); D004791:Enzyme Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010446:Peptide Fragments; D010455:Peptides; D026902:Potassium Channel Blockers; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D009569:Nitric Oxide; C064719:iberiotoxin; D002217:Carbachol; D000803:Angiotensin I; D019001:Nitric Oxide Synthase; C118790:angiotensin I (1-7); D019331:NG-Nitroarginine Methyl Ester