American Journal of Physiology-cell Physiology, 1993
We previously showed that corpus cavernosum smooth muscle cells are connected via gap junctions i... more We previously showed that corpus cavernosum smooth muscle cells are connected via gap junctions in situ and in culture and that a major protein component of these gap junctions is connexin43. To characterize the physiological properties of the gap junctions between corpus cavernosum smooth muscle cells, we now demonstrate that the cells are dye and electrically coupled and describe some of the gating properties of these gap junctional channels at macroscopic and single-channel levels. Junctional conductance (gj) between corporal smooth muscle cells was moderately voltage sensitive; was reduced rapidly, reversibly, and completely by halothane; and was increased by treatment with a tumor-promoting phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] and decreased by isoproterenol. Histograms of unitary junctional currents revealed multiple conductance peaks with events of approximately 90 pS being the most abundant. TPA and phenylephrine produced large increases in relative frequencies of the smaller events, whereas isoproterenol and 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) slightly increased the relative frequencies of the larger events. None of the tested drugs substantially affected the steady-state voltage dependence of gj. These second messenger systems also affected expression of connexin43 by corpus cavernosum smooth muscle cells, as judged by immunoblots. At 6 h of treatment, both TPA- and 8-BrcAMP-treated cultures showed markedly elevated levels of connexin43, whereas at 24 h, the level of connexin43 in TPA-treated cultures had returned to control levels. Together, these data indicate that second messenger molecules involved in penile erection produce changes in gap junction expression and function; it is plausible that these changes could be physiologically relevant in altering and propagating changes in vasomotor tone.
We evaluated the prevalence of andropause symptoms and erectile dysfunction in our infertile popu... more We evaluated the prevalence of andropause symptoms and erectile dysfunction in our infertile population. A total of 302 consecutive men presenting for infertility evaluation and 60 consecutive men with proven fertility seeking vasectomy (controls) were administered the Androgen Deficiency in the Aging Male and Sexual Health Inventory for Men (SHIM) questionnaires. Information regarding other clinical parameters, including seminal parameters, was collected by review of patient charts. Of the 302 infertile men screened, 38% reported significant andropause symptoms and 28% had abnormal SHIM scores. Of the subgroup of infertile men with nonobstructive azoospermia, 25% reported andropause symptoms and 27% had an abnormal SHIM score. In the fertile group 21% reported andropause symptoms and only 11% had an abnormal SHIM score. The prevalence of erectile dysfunction in infertile men was significantly higher than in the fertile controls (p = 0.007). Andropause symptoms and erectile dysfunction are common among infertile men, affecting approximately 38% of this population. This finding suggests that the population of infertile men should be carefully screened to identify and treat those with erectile dysfunction.
Of276 patients who underwent evaluation to determine the cause of hypertension 2 were found to ha... more Of276 patients who underwent evaluation to determine the cause of hypertension 2 were found to have unsuspected renal cell carcinoma. This prevalence of 0.73 per cent is 16 times higher than expected for an age-matched population. Both patients exhibited abnormalities of plasma renin activity before radical nephrectomy but they remained hypertensive postoperatively. The data suggest an unexplained association between hypertension and renal cell carcinoma. Furthermore, abnormalities on excretory urograms in hypertensive people should be defined by selective renal arteriography.
A case of unilateral ureteral obstruction owing to extensive pelvic endometriosis is presented. T... more A case of unilateral ureteral obstruction owing to extensive pelvic endometriosis is presented. There was complete resolution of ureteral obstruction following treatment with synthetic progestin. Sequential assessment of renal function was provided by renal imaging and renograms. It would appear that selected patients with obstructive uropathy may respond favorably to medical management, which would allow for preservation of reproductive capabilities and restoration of renal excretory function. Endometriosis is a common disease in the postpuberal female subject and may produce significant urologic complications. There have been more than 90 cases reported of ureteral obstruction by endometrial tissue during the last decade. 1-7 Obstruction may be caused by intrinsic involvement of the ureteral wall or, more commonly, extrinsic compression by an overlying endometrioma. Therapy has been ureteral resection Fm. 1. Pyelogram. A, normal pelviocaliceal system. B, medial displacement of pelvic portion of right ureter.
Multiple sclerosis (MS) is a devastating degenerative neurological disease that has among its seq... more Multiple sclerosis (MS) is a devastating degenerative neurological disease that has among its sequelae significant urological pathology. Sexual and bladder dysfunction are the most common. Both of these sequelae can have a major effect on a patient's ability to function emotionally and socially. We shall review the pathogenesis of bladder and sexual dysfunction in the MS patient and discuss available diagnostic and treatment modalities.
American Journal of Physiology-Heart and Circulatory Physiology, 1992
Kinetic studies were conducted on the contractile response elicited by phenylephrine (PE) activat... more Kinetic studies were conducted on the contractile response elicited by phenylephrine (PE) activation of the alpha 1-adrenergic receptor subtype in vascular smooth muscle isolated from the corpus cavernosum of impotent men. PE-induced contractions were separated into distinct phasic and tonic components, and the tonic portion was analyzed using a first-order rate equation to determine the maximal rate constant for onset of contraction (kobs max) and the maximum amplitude of the steady-state contractile response (Req max). The kobs max value in tissues from insulin-dependent diabetic patients was significantly greater than that in tissues from either noninsulin-dependent diabetics or nondiabetics. Additionally, the mean kobs max value in older patients (60-70 yr) was significantly greater than the mean kobs max value in younger patients (32-59 yr). Significant diabetes-related, but not age-related, alterations were also found in Req max. The observed changes in contractility resulted ...
THE JOURNAL OF UROLOGY® alterations (p=0.009). Severe ED as quantified by IIEF-5 occurred in 5/9 ... more THE JOURNAL OF UROLOGY® alterations (p=0.009). Severe ED as quantified by IIEF-5 occurred in 5/9 (56%) patients with missense mutations compared to 3/27 (12%) of patients without these sequence abnormalities (p=O.Ol). CONCLUSIONS: Possession of sequence variants in the ATM gene, particularly those that encode for an amino acid substitution, is predictive for the development of erectile dysfunction among patients treated with 125 I prostate brachytherapy.
THE JOURNAL OF UROLOGY® concentrated A and T groups than endothelial cells (p<0,05). Papaverine/ ... more THE JOURNAL OF UROLOGY® concentrated A and T groups than endothelial cells (p<0,05). Papaverine/ phentolamine (A) and tri-mix (T) likewise provoked a decrease in the metabolic activity comparable to the viable cell count. CONCLUSIONS: These in vitro data demonstrate the decrease of endothelial viability under the influence of intracavemous vasoactive agents, underlining a higher and dose-dependent cytotoxic effect of papaverine/phentolamine compared to PGEl. As shown by others (Urology 2002; 59: 155-158) the same but undiluted (!)vasoactive agents produced up to 70% cytotoxicity in cavernosal smooth muscle cell cultures. Cavernosal fibroblasts are much more resistant when exposed to papaverine/phentolamine than penile endothelial cells, which may have an importance for the rate of fibrosis during intracavernous pharmacotherapy.
American Journal of Physiology-Cell Physiology, 1992
Ratio imaging using the calcium-sensitive probe fura-2 was employed to study intracellular calciu... more Ratio imaging using the calcium-sensitive probe fura-2 was employed to study intracellular calcium concentrations and intercellular calcium flux through gap junctions in homogeneous vascular smooth muscle cell cultures derived from the human corpora cavernosa. Microinjection techniques demonstrated that fura-2 free acid was freely diffusible through gap junctions between cultured cells. The resting intracellular calcium level in fura-2-loaded cells was 176.9 +/- 10.5. A robust increase in intracellular calcium was seen in response to both phenylephrine and the calcium ionophore A23187. Microinjection of Ca2+ into individual smooth muscle cells always resulted in significant, although temporally delayed, increases in intracellular calcium levels in adjacent cells; this intercellular calcium flux was reversibly blocked by inhibition of gap junctional communication with 2 mM heptanol. However, although microinjection of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] into individual ...
Despite sparse autonomic innervation, the smooth muscle cells of the corpus cavernosum relax and ... more Despite sparse autonomic innervation, the smooth muscle cells of the corpus cavernosum relax and contract synchronously to achieve penile erection and flaccidity. As with other smooth muscle cell types, the excitation process in the corpora is presumably propagated through gap junctions to allow the diffusion of current-carrying ions and second messenger molecules from cell to cell. Using both molecular and immunocytochemical techniques, we have identified gap junctions between human corporal smooth muscle cells in situ and in culture. Northern analyses demonstrated that corporal smooth muscle cells express the gap junction protein connexin43, but not connexin26 mRNA. Immunoblots showed the presence of connexin43 isoforms, whereas connexin32 was not detected. Immunocytochemical studies in cultured cells identified prominent connexin43 immunoreactive puncta between cells, as well as within the cytoplasm. In addition, gap junction membranes both in situ and in culture were labelled in thin section by anti-connexin43 antibodies using the immunogold technique. We conclude that the presence and distribution of gap junctions in this sparsely innervated tissue may provide an important mechanism of intercellular communication among the smooth muscle cells, and thus play a major role in coordinating tissue contraction and relaxation.
American Journal of Physiology-cell Physiology, 1993
We previously showed that corpus cavernosum smooth muscle cells are connected via gap junctions i... more We previously showed that corpus cavernosum smooth muscle cells are connected via gap junctions in situ and in culture and that a major protein component of these gap junctions is connexin43. To characterize the physiological properties of the gap junctions between corpus cavernosum smooth muscle cells, we now demonstrate that the cells are dye and electrically coupled and describe some of the gating properties of these gap junctional channels at macroscopic and single-channel levels. Junctional conductance (gj) between corporal smooth muscle cells was moderately voltage sensitive; was reduced rapidly, reversibly, and completely by halothane; and was increased by treatment with a tumor-promoting phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] and decreased by isoproterenol. Histograms of unitary junctional currents revealed multiple conductance peaks with events of approximately 90 pS being the most abundant. TPA and phenylephrine produced large increases in relative frequencies of the smaller events, whereas isoproterenol and 8-bromoadenosine 3&#39;,5&#39;-cyclic monophosphate (8-BrcAMP) slightly increased the relative frequencies of the larger events. None of the tested drugs substantially affected the steady-state voltage dependence of gj. These second messenger systems also affected expression of connexin43 by corpus cavernosum smooth muscle cells, as judged by immunoblots. At 6 h of treatment, both TPA- and 8-BrcAMP-treated cultures showed markedly elevated levels of connexin43, whereas at 24 h, the level of connexin43 in TPA-treated cultures had returned to control levels. Together, these data indicate that second messenger molecules involved in penile erection produce changes in gap junction expression and function; it is plausible that these changes could be physiologically relevant in altering and propagating changes in vasomotor tone.
We evaluated the prevalence of andropause symptoms and erectile dysfunction in our infertile popu... more We evaluated the prevalence of andropause symptoms and erectile dysfunction in our infertile population. A total of 302 consecutive men presenting for infertility evaluation and 60 consecutive men with proven fertility seeking vasectomy (controls) were administered the Androgen Deficiency in the Aging Male and Sexual Health Inventory for Men (SHIM) questionnaires. Information regarding other clinical parameters, including seminal parameters, was collected by review of patient charts. Of the 302 infertile men screened, 38% reported significant andropause symptoms and 28% had abnormal SHIM scores. Of the subgroup of infertile men with nonobstructive azoospermia, 25% reported andropause symptoms and 27% had an abnormal SHIM score. In the fertile group 21% reported andropause symptoms and only 11% had an abnormal SHIM score. The prevalence of erectile dysfunction in infertile men was significantly higher than in the fertile controls (p = 0.007). Andropause symptoms and erectile dysfunction are common among infertile men, affecting approximately 38% of this population. This finding suggests that the population of infertile men should be carefully screened to identify and treat those with erectile dysfunction.
Of276 patients who underwent evaluation to determine the cause of hypertension 2 were found to ha... more Of276 patients who underwent evaluation to determine the cause of hypertension 2 were found to have unsuspected renal cell carcinoma. This prevalence of 0.73 per cent is 16 times higher than expected for an age-matched population. Both patients exhibited abnormalities of plasma renin activity before radical nephrectomy but they remained hypertensive postoperatively. The data suggest an unexplained association between hypertension and renal cell carcinoma. Furthermore, abnormalities on excretory urograms in hypertensive people should be defined by selective renal arteriography.
A case of unilateral ureteral obstruction owing to extensive pelvic endometriosis is presented. T... more A case of unilateral ureteral obstruction owing to extensive pelvic endometriosis is presented. There was complete resolution of ureteral obstruction following treatment with synthetic progestin. Sequential assessment of renal function was provided by renal imaging and renograms. It would appear that selected patients with obstructive uropathy may respond favorably to medical management, which would allow for preservation of reproductive capabilities and restoration of renal excretory function. Endometriosis is a common disease in the postpuberal female subject and may produce significant urologic complications. There have been more than 90 cases reported of ureteral obstruction by endometrial tissue during the last decade. 1-7 Obstruction may be caused by intrinsic involvement of the ureteral wall or, more commonly, extrinsic compression by an overlying endometrioma. Therapy has been ureteral resection Fm. 1. Pyelogram. A, normal pelviocaliceal system. B, medial displacement of pelvic portion of right ureter.
Multiple sclerosis (MS) is a devastating degenerative neurological disease that has among its seq... more Multiple sclerosis (MS) is a devastating degenerative neurological disease that has among its sequelae significant urological pathology. Sexual and bladder dysfunction are the most common. Both of these sequelae can have a major effect on a patient's ability to function emotionally and socially. We shall review the pathogenesis of bladder and sexual dysfunction in the MS patient and discuss available diagnostic and treatment modalities.
American Journal of Physiology-Heart and Circulatory Physiology, 1992
Kinetic studies were conducted on the contractile response elicited by phenylephrine (PE) activat... more Kinetic studies were conducted on the contractile response elicited by phenylephrine (PE) activation of the alpha 1-adrenergic receptor subtype in vascular smooth muscle isolated from the corpus cavernosum of impotent men. PE-induced contractions were separated into distinct phasic and tonic components, and the tonic portion was analyzed using a first-order rate equation to determine the maximal rate constant for onset of contraction (kobs max) and the maximum amplitude of the steady-state contractile response (Req max). The kobs max value in tissues from insulin-dependent diabetic patients was significantly greater than that in tissues from either noninsulin-dependent diabetics or nondiabetics. Additionally, the mean kobs max value in older patients (60-70 yr) was significantly greater than the mean kobs max value in younger patients (32-59 yr). Significant diabetes-related, but not age-related, alterations were also found in Req max. The observed changes in contractility resulted ...
THE JOURNAL OF UROLOGY® alterations (p=0.009). Severe ED as quantified by IIEF-5 occurred in 5/9 ... more THE JOURNAL OF UROLOGY® alterations (p=0.009). Severe ED as quantified by IIEF-5 occurred in 5/9 (56%) patients with missense mutations compared to 3/27 (12%) of patients without these sequence abnormalities (p=O.Ol). CONCLUSIONS: Possession of sequence variants in the ATM gene, particularly those that encode for an amino acid substitution, is predictive for the development of erectile dysfunction among patients treated with 125 I prostate brachytherapy.
THE JOURNAL OF UROLOGY® concentrated A and T groups than endothelial cells (p<0,05). Papaverine/ ... more THE JOURNAL OF UROLOGY® concentrated A and T groups than endothelial cells (p<0,05). Papaverine/ phentolamine (A) and tri-mix (T) likewise provoked a decrease in the metabolic activity comparable to the viable cell count. CONCLUSIONS: These in vitro data demonstrate the decrease of endothelial viability under the influence of intracavemous vasoactive agents, underlining a higher and dose-dependent cytotoxic effect of papaverine/phentolamine compared to PGEl. As shown by others (Urology 2002; 59: 155-158) the same but undiluted (!)vasoactive agents produced up to 70% cytotoxicity in cavernosal smooth muscle cell cultures. Cavernosal fibroblasts are much more resistant when exposed to papaverine/phentolamine than penile endothelial cells, which may have an importance for the rate of fibrosis during intracavernous pharmacotherapy.
American Journal of Physiology-Cell Physiology, 1992
Ratio imaging using the calcium-sensitive probe fura-2 was employed to study intracellular calciu... more Ratio imaging using the calcium-sensitive probe fura-2 was employed to study intracellular calcium concentrations and intercellular calcium flux through gap junctions in homogeneous vascular smooth muscle cell cultures derived from the human corpora cavernosa. Microinjection techniques demonstrated that fura-2 free acid was freely diffusible through gap junctions between cultured cells. The resting intracellular calcium level in fura-2-loaded cells was 176.9 +/- 10.5. A robust increase in intracellular calcium was seen in response to both phenylephrine and the calcium ionophore A23187. Microinjection of Ca2+ into individual smooth muscle cells always resulted in significant, although temporally delayed, increases in intracellular calcium levels in adjacent cells; this intercellular calcium flux was reversibly blocked by inhibition of gap junctional communication with 2 mM heptanol. However, although microinjection of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] into individual ...
Despite sparse autonomic innervation, the smooth muscle cells of the corpus cavernosum relax and ... more Despite sparse autonomic innervation, the smooth muscle cells of the corpus cavernosum relax and contract synchronously to achieve penile erection and flaccidity. As with other smooth muscle cell types, the excitation process in the corpora is presumably propagated through gap junctions to allow the diffusion of current-carrying ions and second messenger molecules from cell to cell. Using both molecular and immunocytochemical techniques, we have identified gap junctions between human corporal smooth muscle cells in situ and in culture. Northern analyses demonstrated that corporal smooth muscle cells express the gap junction protein connexin43, but not connexin26 mRNA. Immunoblots showed the presence of connexin43 isoforms, whereas connexin32 was not detected. Immunocytochemical studies in cultured cells identified prominent connexin43 immunoreactive puncta between cells, as well as within the cytoplasm. In addition, gap junction membranes both in situ and in culture were labelled in thin section by anti-connexin43 antibodies using the immunogold technique. We conclude that the presence and distribution of gap junctions in this sparsely innervated tissue may provide an important mechanism of intercellular communication among the smooth muscle cells, and thus play a major role in coordinating tissue contraction and relaxation.
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