TY - JOUR
T1 - Characterization of nitroglycerine induced relaxation in human corpus cavernosum smooth muscle
T2 - Implications to erectile physiology and dysfunction
AU - Christ, G. J.
AU - Kim, D. C.
AU - Taub, H. C.
AU - Gondre, C. M.
AU - Melman, A.
PY - 1995
Y1 - 1995
N2 - The importance of the nitric oxide - guanylate cyclase - cGMP system in modulating corporal smooth muscle tone and penile erection has been amply demonstrated. The goal of these studies was to evaluate the possibility that age- or disease-related alterations in human corporal smooth muscle responsivity to activation of this pathway might play a role in the etiology of erectile dysfunction. Thus, we utilized a previously described heuristic model to assess the kinetic and steady-state characteristics of relaxation of precontracted isolated corporal tissue strips elicited by nitroglycerine (NTG). Studies were conducted on corporal tissue strips excised from 26 patients with organic erectile dysfunction, and 7 patients with documented erections. For the purposes of statistical analysis the impotent patient population was stratified into two age groups (A, ≤59 years; B, ≥60 years) and further subdivided into two diagnostic categories, diabetic and nondiabetic patients, respectively. In ~ 75% of precontracted corporal tissue strips derived from impotent patients (contracted to ~ 75% of maximum with phenylephrine), the NTG-induced response was biphasic, consisting of a rapid relaxation response that reached steady state before onset of a more slowly developing regaining of tension, termed the desensitization response. In contrast, a biphasic response was observed much less frequently (~ 30%) in corporal tissue strips derived from a potent patient population (p < 0.0001). Statistical analysis revealed significant heterogeneity among corporal tissue strips derived from patients with organic erectile dysfunction, with respect to both the kinetic and steady-state characteristics of the NTG-induced relaxation and desensitization responses. In particular, the maximal rate constant for both NTG-induced relaxation (k(relmax) p < 0.01) and desensitization (k(des); p < 0.03) responses was significantly greater in corporal tissue strips excised from diabetic than nondiabetic patients. Furthermore, the EC50 for NTG-induced relaxation of precontracted corporal smooth muscle strips from potent patients ( ~ 25 nM) was 0.90 log unit less than that for equivalently contracted corporal smooth muscle strips derived from impotent patients (~ 180 nM; p < 0.03). Such observations suggest that alterations in corporal smooth muscle responsivity to activation of the guanylate cyclase - cGMP pathway, per se, may be a characteristic of organic erectile dysfunction. In the absence of compensatory changes in other vasodilatory mechanisms, this may contribute to incomplete corporal smooth muscle relaxation and the etiology of erectile dysfunction in some patients.
AB - The importance of the nitric oxide - guanylate cyclase - cGMP system in modulating corporal smooth muscle tone and penile erection has been amply demonstrated. The goal of these studies was to evaluate the possibility that age- or disease-related alterations in human corporal smooth muscle responsivity to activation of this pathway might play a role in the etiology of erectile dysfunction. Thus, we utilized a previously described heuristic model to assess the kinetic and steady-state characteristics of relaxation of precontracted isolated corporal tissue strips elicited by nitroglycerine (NTG). Studies were conducted on corporal tissue strips excised from 26 patients with organic erectile dysfunction, and 7 patients with documented erections. For the purposes of statistical analysis the impotent patient population was stratified into two age groups (A, ≤59 years; B, ≥60 years) and further subdivided into two diagnostic categories, diabetic and nondiabetic patients, respectively. In ~ 75% of precontracted corporal tissue strips derived from impotent patients (contracted to ~ 75% of maximum with phenylephrine), the NTG-induced response was biphasic, consisting of a rapid relaxation response that reached steady state before onset of a more slowly developing regaining of tension, termed the desensitization response. In contrast, a biphasic response was observed much less frequently (~ 30%) in corporal tissue strips derived from a potent patient population (p < 0.0001). Statistical analysis revealed significant heterogeneity among corporal tissue strips derived from patients with organic erectile dysfunction, with respect to both the kinetic and steady-state characteristics of the NTG-induced relaxation and desensitization responses. In particular, the maximal rate constant for both NTG-induced relaxation (k(relmax) p < 0.01) and desensitization (k(des); p < 0.03) responses was significantly greater in corporal tissue strips excised from diabetic than nondiabetic patients. Furthermore, the EC50 for NTG-induced relaxation of precontracted corporal smooth muscle strips from potent patients ( ~ 25 nM) was 0.90 log unit less than that for equivalently contracted corporal smooth muscle strips derived from impotent patients (~ 180 nM; p < 0.03). Such observations suggest that alterations in corporal smooth muscle responsivity to activation of the guanylate cyclase - cGMP pathway, per se, may be a characteristic of organic erectile dysfunction. In the absence of compensatory changes in other vasodilatory mechanisms, this may contribute to incomplete corporal smooth muscle relaxation and the etiology of erectile dysfunction in some patients.
KW - Corporal smooth muscle
KW - Desensitization
KW - Guanylate cyclase
KW - Nitroglycerine
KW - Relaxation
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U2 - 10.1139/y95-735
DO - 10.1139/y95-735
M3 - Article
C2 - 8834485
AN - SCOPUS:0029554131
SN - 0008-4212
VL - 73
SP - 1714
EP - 1726
JO - Canadian Journal of Physiology and Pharmacology
JF - Canadian Journal of Physiology and Pharmacology
IS - 12
ER -