0022-534 7/79/1214-0419$02. 00/0 Vol. 121, April
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
Printed in U.S.A.
THE POSSIBLE ROLE OF THE CATECHOLAMINES OF THE CORPORA IN PENILE ERECTION ARNOLD MELMAN*
AND
DAVID HENRY
From the Departments of Urology, Pharmacology and Medicine, Indianapolis Veterans Administration Hospital, Indiana University Medical Center, Lilly Laboratory for Clinical Research, Indianapolis, Indiana
ABSTRACT
The etiolog-y- of impotence, which affects 50 per cent of the men with diabetes, is unknown. The neurotransmitter (norepinephrine) released. from adrenergic neurons is thought to be the most direct regulator of vascular smooth muscle. We have measured the norepinephrine content of the erectile tissue of diabetic men. Our results indicate the presence of a dual neural regulator mechanism of the corpora that controls erection. Impotence is a symptom in nearly 50 per cent of the estimated 1.5 million male subjects in the United States who have diabetes mellitus. 1 Eighty-eight per cent of these people with diabetes and erectile impotence also have a polyneuropathy. 2 In addition, dysfunction of the autonomic nervous system has been a long-recognized concomitant of diabetes mellitus. 3 The precise mechanism of human penile erection in health and its dysfunction in disease remain undefined. In the broadest terms erection can be conceived mechanistically as autonomic neuronal stimulation of the vascular tissue of the penis with resultant vasodilatation and filling of the intratrabecular spaces of the corpora cavernosa with blood. Classical teaching holds that erection is predominantly a parasympathetic function. This theory has been extant since 1863, when Eckhardt electrically stimulated the pelvic nerves of dogs and, thereby, caused an erection presumably by increasing penile vascular flow. 4 The nerves that he stimulated, designated the nervi erigentes, are preganglionic parasympathetic neurons arising from the second, third and fourth sacral segments. In 1947 Root and Bard demonstrated that the adrenergic nerves also are a factor in penile erection.' In their experiments surgical ablation of the lower sacral spinal cord (L4 to 83) did not cause cessation of erection in male cats. However, when the thoracic sympathetic chain was excised the animals were no longer capable of erection. Additional support for adrenergic stimulation was reported by Whitelaw and Smithwick, who performed surgical sympathectomies in patients with severe hypertension.'; Disturbance of erectile function was demonstrated in 57 per cent of the patients undergoing sympathetic ablation of T2 through T12 and in 63 per cent of the patients undergoing the operation in Ll through L3. Impotence is an important problem in men with diabetes and, because the role of the sympathetic (adrenergic) neurons in penile erection is undefined, we have measured the norepinephrine content of the erectile tissue of diabetic patients undergoing penile surgery. N orepinephrine has been shown to be the chemical neurotransmitter of the peripheral sympathetic nervous system. 7 The substance is concentrated, stored and released from vesicles contained in the terminal axons of sympathetic neurons." The axons form an autonomic ground plexus surrounding blood vessels and smooth muscle cells. '1 The norepinephrine concentration in tissue reflects the density of sympathetic innervation of that tissue. 7
METHODS
The spongy erectile tissue of the penile corpora was obtained from 28 patients during placement of a penile prosthesis or total penectomy. Eleven patients had diabetes. Two other g-rnups included men with impotence resulting from a radical operation or perineal trauma and spinal cord injury. Two patients could achieve erections but with severe chordee as a result of Peyronie's disease. Tissue from these 2 patients and 2 potent patients undergoing penectomy served as controls. After removal the tissue was frozen immediately and later analyzed for norepinephrine concentration by a radioenzymatic technique. 10 No clinical evidence of aortofemoral occlusive disease as the cause of impotence was present in any of the patients.
Accepted for publication July 26, 1978. Read at annual meeting of American Urological Association, D. C . May 21-25. 1978. address: Department of Beth Israel Medicai Center 10 :Nathan D. Perlman Place. Nev.: l~evv York 10003. 1
41~
RESULTS
Tissue obtained from within the corpora macroscopically was indistinguishable between the experimental groups. There was no difference between the blood loss from the open corpora of the group at the time of operation. Quantitative measurements of the norepinephrine content of the erectile tissue were summarized (table and fig. 1). There is a significant diminution of norepinephrine concentration in those patients with insulin-dependent diabetes. Those patients form the basis for the incidence oflow concentrations ofnorepinephrine in patients without erections (fig. 1). The norepinephrine concentration in all diabetic patients who required insulin was 71.4 ± 25.3 pg./mg. wet weight tissue. Within this group, however, 1 patient with a norepinephrine concentration of 121 pg./mg. tissue had severe chordee from Peyronie's disease but was able to have erections. The mean concentration in the remaining 4 patients was 59.0 ± 28.4 pg./mg. wet weight. These results are significantly different from the normal mean of 580.6 pg./mg. weight of tissue in normal men (p
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
Printed in U.S.A.
THE POSSIBLE ROLE OF THE CATECHOLAMINES OF THE CORPORA IN PENILE ERECTION ARNOLD MELMAN*
AND
DAVID HENRY
From the Departments of Urology, Pharmacology and Medicine, Indianapolis Veterans Administration Hospital, Indiana University Medical Center, Lilly Laboratory for Clinical Research, Indianapolis, Indiana
ABSTRACT
The etiolog-y- of impotence, which affects 50 per cent of the men with diabetes, is unknown. The neurotransmitter (norepinephrine) released. from adrenergic neurons is thought to be the most direct regulator of vascular smooth muscle. We have measured the norepinephrine content of the erectile tissue of diabetic men. Our results indicate the presence of a dual neural regulator mechanism of the corpora that controls erection. Impotence is a symptom in nearly 50 per cent of the estimated 1.5 million male subjects in the United States who have diabetes mellitus. 1 Eighty-eight per cent of these people with diabetes and erectile impotence also have a polyneuropathy. 2 In addition, dysfunction of the autonomic nervous system has been a long-recognized concomitant of diabetes mellitus. 3 The precise mechanism of human penile erection in health and its dysfunction in disease remain undefined. In the broadest terms erection can be conceived mechanistically as autonomic neuronal stimulation of the vascular tissue of the penis with resultant vasodilatation and filling of the intratrabecular spaces of the corpora cavernosa with blood. Classical teaching holds that erection is predominantly a parasympathetic function. This theory has been extant since 1863, when Eckhardt electrically stimulated the pelvic nerves of dogs and, thereby, caused an erection presumably by increasing penile vascular flow. 4 The nerves that he stimulated, designated the nervi erigentes, are preganglionic parasympathetic neurons arising from the second, third and fourth sacral segments. In 1947 Root and Bard demonstrated that the adrenergic nerves also are a factor in penile erection.' In their experiments surgical ablation of the lower sacral spinal cord (L4 to 83) did not cause cessation of erection in male cats. However, when the thoracic sympathetic chain was excised the animals were no longer capable of erection. Additional support for adrenergic stimulation was reported by Whitelaw and Smithwick, who performed surgical sympathectomies in patients with severe hypertension.'; Disturbance of erectile function was demonstrated in 57 per cent of the patients undergoing sympathetic ablation of T2 through T12 and in 63 per cent of the patients undergoing the operation in Ll through L3. Impotence is an important problem in men with diabetes and, because the role of the sympathetic (adrenergic) neurons in penile erection is undefined, we have measured the norepinephrine content of the erectile tissue of diabetic patients undergoing penile surgery. N orepinephrine has been shown to be the chemical neurotransmitter of the peripheral sympathetic nervous system. 7 The substance is concentrated, stored and released from vesicles contained in the terminal axons of sympathetic neurons." The axons form an autonomic ground plexus surrounding blood vessels and smooth muscle cells. '1 The norepinephrine concentration in tissue reflects the density of sympathetic innervation of that tissue. 7
METHODS
The spongy erectile tissue of the penile corpora was obtained from 28 patients during placement of a penile prosthesis or total penectomy. Eleven patients had diabetes. Two other g-rnups included men with impotence resulting from a radical operation or perineal trauma and spinal cord injury. Two patients could achieve erections but with severe chordee as a result of Peyronie's disease. Tissue from these 2 patients and 2 potent patients undergoing penectomy served as controls. After removal the tissue was frozen immediately and later analyzed for norepinephrine concentration by a radioenzymatic technique. 10 No clinical evidence of aortofemoral occlusive disease as the cause of impotence was present in any of the patients.
Accepted for publication July 26, 1978. Read at annual meeting of American Urological Association, D. C . May 21-25. 1978. address: Department of Beth Israel Medicai Center 10 :Nathan D. Perlman Place. Nev.: l~evv York 10003. 1
41~
RESULTS
Tissue obtained from within the corpora macroscopically was indistinguishable between the experimental groups. There was no difference between the blood loss from the open corpora of the group at the time of operation. Quantitative measurements of the norepinephrine content of the erectile tissue were summarized (table and fig. 1). There is a significant diminution of norepinephrine concentration in those patients with insulin-dependent diabetes. Those patients form the basis for the incidence oflow concentrations ofnorepinephrine in patients without erections (fig. 1). The norepinephrine concentration in all diabetic patients who required insulin was 71.4 ± 25.3 pg./mg. wet weight tissue. Within this group, however, 1 patient with a norepinephrine concentration of 121 pg./mg. tissue had severe chordee from Peyronie's disease but was able to have erections. The mean concentration in the remaining 4 patients was 59.0 ± 28.4 pg./mg. wet weight. These results are significantly different from the normal mean of 580.6 pg./mg. weight of tissue in normal men (p
