Effects Of Endopeptidase Inhibition Research Articles

Effects of endopeptidase inhibition on the relaxation response of isolated human penile erectile tissue to vasoactive peptides.

Peptides, such as CNP, CGRP and VIP, are involved in the function of male penile erectile tissue. Tissue levels of said peptides are controlled by the endopeptidase enzymes. Theoretically, the inhibition of the degradation of CNP, CGRP and/or VIP should result in an enhancement in penile smooth muscle relaxation. The effects were investigated of CNP or VIP (0.1nm-1μm), without and following pre-exposure of the tissue to a threshold concentration of the endopeptidase inhibitor KC 12615 (10μm, for 20min), on the reversion of tension induced by means of electrical field stimulation. Drug effects on the production of cyclic AMP/GMP were also evaluated. Neither KC 12615, CNP and VIP nor the combination of CNP plus KC 12615 or VIP plus KC 12615 increased the response of the tissue to EFS. While no effects were observed of a pre-exposure of the tissue to KC 12615 on the production of cyclic AMP in the presence of VIP, an enhancement was registered in the accumulation of cyclic AMP in the presence of CNP plus KC 12615. Further studies are indicated to investigate whether endopeptidase inhibitors might tend to be more effective in tissues affected by a decreased local production of vasoactive peptides.

Effects of Endopeptidase Inhibition on the Contraction–Relaxation Response of Isolated Human Vaginal Tissue

INTRODUCTION.: Vasoactive peptides, such as bradykinin, C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP), and endothelin 1 (ET-1), are assumed to be involved in the control of female genital vascular and nonvascular smooth muscle. Tissue levels of said peptides are controlled by the activity of endopeptidase enzymes. Theoretically, in female genital tissues, inhibiting the degradation of bradykinin, CNP, and VIP, or the conversion of Big ET-1 into ET-1 should result in an enhancement in smooth muscle relaxation and, thus, an improvement in sexual response. AIM.: Elucidate the effects of the endopeptidase inhibitor KC 12615 on the contraction/relaxation response of isolated human vaginal smooth muscle to Big ET-1, bradykinin, CNP, or VIP. METHODS.: Tissue bath experiments were carried out to ascertain the responses of human vaginal tissue challenged by ET-1 (0.1 μM) to increasing concentrations of bradykinin, CNP, and VIP (0.01 μM, 0.1 μM, and 1 μM, respectively). The effects were also evaluated following preexposure to KC 12615 (10 μM, for 20 minutes). MAIN OUTCOME MEASURES.: Measure the effects of KC 12615 on the relaxation of isolated human vaginal smooth muscle brought about by bradykinin, CNP, or VIP and the contraction mediated by Big ET-1. RESULTS.: The tension induced by ET-1 was reversed by bradykinin, CNP, or VIP (-25 ± 6.6%, -13.3 ± 2.2%, and -17.6 ± 10%, respectively). Big ET-1 induced contraction of the vaginal tissue. Preexposure of the tissue to KC 12615 increased the relaxation exerted by bradykinin, CNP, or VIP (to -39.2 ± 5.8%, -40.7 ± 7.3%, and -44.6 ± 19%, respectively). The contraction induced by Big ET-1 was attenuated in the presence of KC 12615 (to approximately 25% of the initial response). CONCLUSION.: Inhibition of endopeptidase activity can antagonize the contraction of human vaginal tissue induced by Big ET-1 and increase the relaxation induced by vasoactive endogenous peptides.

Contribution of ANP to plasma protein escape during VE: effects of thiorphan and atrial appendectomy.

The effects of endopeptidase inhibition and right atrial appendectomy (AA) on plasma immunoreactive atrial natriuretic peptide (irANP) concentrations and extravascular accumulation of 131I-labeled bovine serum albumin (CBSA) during volume expansion (VE) were examined in pentobarbital sodium-anesthetized rats (n = 5 per group). Compared with controls, infusion of isoncotic albumin (30 ml/kg) increased central venous pressure (CVP) by 5.5 mmHg, plasma irANP by 7-fold, and CBSA in multiple tissues by 1.6- to 4-fold (P < or = 0.05). Inhibition of ANP metabolism with thiorphan (40 mg/kg) had no effect in control animals but increased plasma irANP (+118%) and CBSA (+30-100%) compared with VE alone (P < or = 0.05). Likewise, interference with ANP release by AA reduced plasma irANP (-80%) and CBSA (-30 to -80%) response to VE in parallel (P < or = 0.05). The peak increase in CVP during VE was not affected by either of these manipulations. It is concluded that endogenous ANP increases plasma protein extravasation independent of volume and pressure disturbances during acute intravascular expansion.