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Effects of enalapril on human sperm motility
CONTRACEPTION
EFFECTS OF ENALAPRIL ON HUMAN SPERM MOTILITY
W D Ratnasooriya
and K G I Jayawardena
Department of Zoology, University of Colombo, Colombo 3, Sri Lanka
R l4 Wadsworth Department of Physiology and Pharmacology, University of Strathclyde, Glasgow UK
ABSTRACT The angiotensin converting enzyme inhibitor, enalapril, reduced the motility The concentrations producing 50% inhibition of washed human spermatozoa. were: (percentage motility) 11.6f2.6 mM, (average forward velocity) B.Ot1.5 mM and (motility index) 8.5fZ.l mM (mean + s.e.m.). Enalapril 20 mM prevented all forward movement and reduced percentage motility to an extremely low level. Motility was reduced within 20 set of addition and little further change occurred during a 60-min incubation period. Inhibition of percentage motility by enalapril was reversible with a 5-min washing procedure following a S-min incubation period, but not following a 60-min incubation period. Enalapril 20 mM did not impair plasma membrane integrity (hypoosmotic swelling test) or viability (nigrosin-eosin stain). It is concluded that the antimotility effects of enalapril are not caused by inhibition of angiotensin converting enzyme, but may be of interest in the search for new spermicidal agents. Submitted for publication March 24, 1989 Accepted for publication November 1, 1989
FEBRUARY 1990 VOL. 41 NO. 2
213
CONTRACEPTION
INTRODUCTION Several studies have shown the presence of angiotensin converting enzyme (ACE) in the male reproductive tract including the.testes, epididymis, Recently ACE has also been "as deferens and prostate (1,2,3). However, the shown to be present in spermatozoa (4,5) and in semen (6). precise role of ACE in male reproductive function is unknown. The ACE inhibitor captopril impairs motility of human spermatozoa (7). Moreover,athe clinically effective male antifertility agent gossypol reduces sperm motility and inhibits ACE (8). It is possible that ACE may play a role in the regulation of sperm motility and also that captopril or a related compound may be worth evaluating as a potential contraceptive agent. This paper enalapril,
reports the antimotility which is the most potent
effect, on human spermatozoa, of ACE inhibitor in clinical use (9).
METHODS A single semen sample was obtained from each of 9 healthy donors (25-30 years) followingo3-5 days of sexual abstinence. The specimens were allowed to liquefy at 31 C for 15-25 min, and then standard semen analysis was undertaken under phase contrast microscopy according to the guidelines established by the World Hea&,th Organisation (10). All specimens used had a sperm concentration 340 x 10 spermatoza/ml, motility of >, 40% and normal morphology of 3 40%. The spermatozoa were isolated from seminal plasma by three cycles of centrifugation (500 g for 5 min) with 9 ml volumgs of medium BWW (11) and were finally resuspended at a density of 20 x 10 spermatozoa/ml for the evaluation of drug effects. Enalapril was dissolved in BWW medium, 500 ~1 of washed spermatozoa suspension was placed in Falcon tubes and a" equal volume of either the vehicle (BWW) or enalapril dissolved in BWW was added (final concentration of enalapril 2.5, 5.0, 10.0 or 20.0 mM), mixed well and the time was recorded. The suspensions were incubated for 60 min and 10 ~1 samples were transferred onto separate clean glass slides (316C) and covered with a cover glass (22 x 22 mm). The percentage motile spermatozoa (10) and the average forward velocity (12) were determined at each concentration and time point under phase contrast microscopy using a squared grid and a crossed micrometer,respectively. The motility index was then calculated as the product of percentage motility and velocity (13). The spermatozoa incubated with 20mM enalapril for 5 min and 60 min were washed with BWW for 5 min and the above mentioned motility parameters were reinvestigated. Further samples of enalapril-treated (20 mM) and control spermatozoa were subjected to the hypoosmotic swelling test (14) and to the nigrosin-eosin stain technique at 5 min and 60 min, respectively. The concentration of enalapril that decreased the percentage spermatozoa motility, the average forward velocity and the motility index to 50% of control (EC ) was obtained from log concentration response curves. 50 Results are given as means ? s.e.m. using Student's Paired t-test.
214
Statistical
comparisons
were made
FEBRUARY 1990 VOL. 41 NO. 2
CONTRACEPTION
RESULTS At a concentration of Enalapril inhibited the motility of human spermatozoa. 10 mM, enalapril inhibited average forward velocit-y, percentage motility and Motility was found to be inhibited immediately motility index (Figure). after addition of enalapril and there was little change in the level of At the higher concentration of 20 inhibition during the subsequent 60 min. mM, enalapril caused complete abolition of forward velocity and motility I" none of index, and the percentage motility was extremely low (Figure) the suspensions treated with enalapril was there any floculatio" or values for enalapril were: (inhibition of agglutination. percentage motilT!y)ET??6 i 2.6 mM , (average forward velocity) 8.0 + 1.5 ml4 and (motility index) 8.5 C 2.1 mM. The effects of enalapril on forward velocity and on motility index appeared not to be reversible on washing. nowever, the percentage motility was restored by a 5-min wash to 6720.1% of control motility When ("=9, PcO.05) when prior incubation with enalapril had been 5 min. enalapril had been in contact with the spermatozoa for 60 min. a 5-min wash did not retore motility (7.5+_9.3% of control percentage motility, n=9, not significantly different from enalapril-treated suspensions). Enalapril 20 mM had no effect on viability (nigrosin-eosin stain technique) At 60 min the or hypoosmotic swelling, after either 5 or 60 min contact. viability of control suspensions was 66f4%, and of enalapril 20 mM suspensions was 68+5%. At 60 min the control samples contained 61f6% swollen spermatozoa and the enalapril 20 mM suspension contained 53+3% swollen spermatozoa ("=9, not significantly different). DISCUSSION This study demonstrates a concentration-related antimotility effect of the ACE inhibitor enalapril in washed human spermatozoa -in vitro. However, the potency ratio of the ACE inhibitors captopril and enalapril for reduction of motility of human spermatozoa is about 0.5 (7) and for inhibitors of ACE effect of enalapril is not about 0.1 (15). Thus, the sperm immobilization likely to be the result of inhibition of ACE, which has been shown to be present on spermatozoa (4,5). The ACE inhibitors block both forms of ACE, and also inhibit other dipeptidyl carboxypeptidases (16). Other actions of enalapril that could mediate its antimotility effect include reducing cyclic AMP concentration (17), reducing bradykinin levels (la), or increasing These effects would be expected to have a prostaglandin synthesis (19). deleterious effect on sperm function (20). Several drugs immobilize Since enalapril spermatozoa through stabilization of the cell membrane (21). Placzek is hydrophilic (22), it is unlikely to stabilize the sperm membrane. et al. (0) reported that neither enalapril nor captopril affects sperm OU?Z used were too low. motility, but in that study the concentrations results show that when the concentration of enalapril or captopril is increased slightly above the maximum used by Placzek et al., a clear antimotility effect is see". Of the semen parameters measured, enalapril is more specific than captopril At concentrations producing complete as a" inhibitor of sperm motility. abolition of forward velocity, enalapril did not impair membrane function or
FEBRUARY 1990VOL. 41 NO. 2
215
CONTRACEPTION
..
.
I.
! ! ,*
-!
-‘I
w,_ -;,“-
..&
:::
0 ( swh)
216
1113013A
XXNI
~11lIlCd
FEBRUARY 1990 VOL. 41 NO. 2
CONTRACEPTION
viability as judged by the hypoosmotic swelling test stain test. By contrast, captopril impairs membrane with loss of movement (7).
and the nigrosin-eosin function in parallel
A close relationship exists between sperm movement and fertility (23). Ejaculates with spermatozoa having low percentage motility (24), subnormal forward velocities (23) and low motility indices (25) are less likely to fertilize ova. The fact that these three vital parameters of motility were concomitantly impaired by enalapril makes it, or a derivative, worth investigating further as a vaginal contraceptive. Ideally, such a derivative should be, compared to enalapril, less easily reversed by washing in, for example, cervical fluid.
ACKNOWLEDGEMENTS Mr. G A S Premakumara
for
technical
assistance.
REFERENCES 1.
Jaiswal A, Joshi P, Kumar converting enzyme in the Andrologia 1984; 16:410-6.
M U, Panda J N, Singh L N. Angiotensin testes, and epididymis of mammals.
2.
Strittmatter S M, Snyder male reproductive system: captoprjl. Endocrinology
3.
Cushman D W, Cheung enzyme in tissues 250:261-5.
4.
Yotsumoto H, sat0 s, Shibuya M. Localization of angiotensin converting enzyme (dipeptidyl carboxypeptidase) in swine sperm by immunofluorescence. Life Sci 1984; 35:1257-61.
5.
Scandellari C. Foresta Indino Manoni C, M, F, human spermatozoa and its Angiotensin-converting enzyme content of release during capacitation. Fertil Steril 1987; 47:1000-3.
6.
Hohlbrugger G, Pschorr enzyme in the ejaculate Steril 1984; 41:324-5.
7.
Ratnasooriya effect of 16:935-6.
8.
ACE-inhihitors Placzek R, Krassnigg F, Schill W-B. Effect of and alpha calmodulin antagonists, acetycholine receptor blocking, Arch Anrdol receptor blocking agents on motility of human sperm. 1988; 21:1-10.
S H. Angiotensin-converting enzyme in !jhe Autoradiographic visualization with [ HI1984; 115:2332-41.
converting H S. Concentration of angiotensin 1971; of the rat. Biochem Biophys Acta
J, Dahlheim of fertile
W D, Rathnayaka captopril on human
FEBRUARY 1990 VOL. 41 NO. 2
M. Angiotensin and infertile
I
converting Fertil me".
inhibitory P C, Wadsworth R M. The Hed Sci Res 1988; sperm motility.
217
CONTRACEPTION
9.
Gomez H J, Cirillo, U J and Irui" J D. Enalapril: pharmacology. Drugs 1985; 30(1):13-24.
a review
of human
10. Beleey M A, Eliasson R, Gallegos A J et- al. (eds.). Laboratory MUCUS Manual for the Examination of Human Semen and Semen-Cervical Interaction. (WHO) Singapore: Press Concern, 1980; l-23. D G. The culture of mouse 11. Biggers J D, Whitten W K, Whittingham eggs in vitro. In: Daniel J C (ed.) Methods in mammalian embyology. San Francisco Freeman, 1971; 86. 12. Daunter B, biochemistry
Hill R, Hennessey 1. Andrologia 1981;
J, Mackay 13:131-41.
E
U. Seminal
plasma
13. Keel B A, Webster B W, Roberts D K. Effects of cryopreservation on human spermatozoa. the motility characteristics of J Reprod Fert 1987; 81:213-220. 14. Jeyendran R S, Van der Ven H H, Perez-Peloez M, Crabo B G, Zeneveld L J D. Development of an assay to assess the functional integrity of the human sperm membrane and its relationship to other semen characteristics. J Reprod Fert 1984; 70:219-28. 15. Laragh J H. Conceptual diagnostic and therapeutic dimensions of renin-system profiling of hypertensive disorders and of congestive heart failure: four new research frontiers. In: Doyle A E, Beam A G (eds.). Hypertension angiotensin system: Therapeutic and the approaches. New York: Raven Press, 1983; 44-76. 16. Soffer R L. Some thoughts' about inhibition of the angiotensin system. In: the Doyle A E, Bean A G (eds.). Hypertension and angiotensin system: Therapeutic New York: Raven Press, approaches. 1983:179-89. 17.
Geiger H, Bahner U, Heidland A. Effect of Palkouits M, angiotensin-converting enzyme inhibitors captopril and enalapril on CAMP content of specific brain areas in spontaneously hypertensive rats. Clin Expt Pharmac Physiol 1987; 14:327-32.
18. Schill W B, Haberland G L. Kinin-induced motility. Hoppe Seylers Physiol Chem 1974;
enhancement 325:229-31.
of
sperm
19. Zusman R M. Renin and non-renin-mediated antihypertensive actions Kidney Int 1984; 25:969-83. of converting enzyme inhibitors. 20. Lessing J B, Paz G F, Peyser M R, Homonnai 2 T, Brenner S H, Weiss G. Lxboratory efforts to improve motility of human sperm. Seminars Reprod Endocri" 1987; 5:91-E. Turner 21. Hong C Y, P. Influence of immobilizing effect of P-adrenoceptor Pharmacol 1982; 14:269-72.
218
lipid solubility on the sperm blocking drugs. Br J Clin
FEBRUARY 1990 VOL. 41 NO. 2
CONTRACEPTION
22. Patch&t In: Doyle A E, Bear-n A G A A. The design of enalapril. (eds.). Hypertension system: Therapeutic angiotensin and the approaches. New York: Raven Press, 1983:155-65. 23. Hartman H G. Correlation Steril 1965; 16:632-44. 24. Amelar R D, Dubin 1980; 34:197-215.
among
criteria
L, Schoenfeld
of
C. Sperm
25. Mathur S, Carlton M, Ziegler J, Rust P Fertil computerized sperm motion analysis.
FEBRUARY 1990 VOL. 41 NO. 2
semen
motility.
quality.
Fertil
Fertil
Steril
H 0. A F, Williamson Steril 1986; 46:484-88.
219
EFFECTS OF ENALAPRIL ON HUMAN SPERM MOTILITY
W D Ratnasooriya
and K G I Jayawardena
Department of Zoology, University of Colombo, Colombo 3, Sri Lanka
R l4 Wadsworth Department of Physiology and Pharmacology, University of Strathclyde, Glasgow UK
ABSTRACT The angiotensin converting enzyme inhibitor, enalapril, reduced the motility The concentrations producing 50% inhibition of washed human spermatozoa. were: (percentage motility) 11.6f2.6 mM, (average forward velocity) B.Ot1.5 mM and (motility index) 8.5fZ.l mM (mean + s.e.m.). Enalapril 20 mM prevented all forward movement and reduced percentage motility to an extremely low level. Motility was reduced within 20 set of addition and little further change occurred during a 60-min incubation period. Inhibition of percentage motility by enalapril was reversible with a 5-min washing procedure following a S-min incubation period, but not following a 60-min incubation period. Enalapril 20 mM did not impair plasma membrane integrity (hypoosmotic swelling test) or viability (nigrosin-eosin stain). It is concluded that the antimotility effects of enalapril are not caused by inhibition of angiotensin converting enzyme, but may be of interest in the search for new spermicidal agents. Submitted for publication March 24, 1989 Accepted for publication November 1, 1989
FEBRUARY 1990 VOL. 41 NO. 2
213
CONTRACEPTION
INTRODUCTION Several studies have shown the presence of angiotensin converting enzyme (ACE) in the male reproductive tract including the.testes, epididymis, Recently ACE has also been "as deferens and prostate (1,2,3). However, the shown to be present in spermatozoa (4,5) and in semen (6). precise role of ACE in male reproductive function is unknown. The ACE inhibitor captopril impairs motility of human spermatozoa (7). Moreover,athe clinically effective male antifertility agent gossypol reduces sperm motility and inhibits ACE (8). It is possible that ACE may play a role in the regulation of sperm motility and also that captopril or a related compound may be worth evaluating as a potential contraceptive agent. This paper enalapril,
reports the antimotility which is the most potent
effect, on human spermatozoa, of ACE inhibitor in clinical use (9).
METHODS A single semen sample was obtained from each of 9 healthy donors (25-30 years) followingo3-5 days of sexual abstinence. The specimens were allowed to liquefy at 31 C for 15-25 min, and then standard semen analysis was undertaken under phase contrast microscopy according to the guidelines established by the World Hea&,th Organisation (10). All specimens used had a sperm concentration 340 x 10 spermatoza/ml, motility of >, 40% and normal morphology of 3 40%. The spermatozoa were isolated from seminal plasma by three cycles of centrifugation (500 g for 5 min) with 9 ml volumgs of medium BWW (11) and were finally resuspended at a density of 20 x 10 spermatozoa/ml for the evaluation of drug effects. Enalapril was dissolved in BWW medium, 500 ~1 of washed spermatozoa suspension was placed in Falcon tubes and a" equal volume of either the vehicle (BWW) or enalapril dissolved in BWW was added (final concentration of enalapril 2.5, 5.0, 10.0 or 20.0 mM), mixed well and the time was recorded. The suspensions were incubated for 60 min and 10 ~1 samples were transferred onto separate clean glass slides (316C) and covered with a cover glass (22 x 22 mm). The percentage motile spermatozoa (10) and the average forward velocity (12) were determined at each concentration and time point under phase contrast microscopy using a squared grid and a crossed micrometer,respectively. The motility index was then calculated as the product of percentage motility and velocity (13). The spermatozoa incubated with 20mM enalapril for 5 min and 60 min were washed with BWW for 5 min and the above mentioned motility parameters were reinvestigated. Further samples of enalapril-treated (20 mM) and control spermatozoa were subjected to the hypoosmotic swelling test (14) and to the nigrosin-eosin stain technique at 5 min and 60 min, respectively. The concentration of enalapril that decreased the percentage spermatozoa motility, the average forward velocity and the motility index to 50% of control (EC ) was obtained from log concentration response curves. 50 Results are given as means ? s.e.m. using Student's Paired t-test.
214
Statistical
comparisons
were made
FEBRUARY 1990 VOL. 41 NO. 2
CONTRACEPTION
RESULTS At a concentration of Enalapril inhibited the motility of human spermatozoa. 10 mM, enalapril inhibited average forward velocit-y, percentage motility and Motility was found to be inhibited immediately motility index (Figure). after addition of enalapril and there was little change in the level of At the higher concentration of 20 inhibition during the subsequent 60 min. mM, enalapril caused complete abolition of forward velocity and motility I" none of index, and the percentage motility was extremely low (Figure) the suspensions treated with enalapril was there any floculatio" or values for enalapril were: (inhibition of agglutination. percentage motilT!y)ET??6 i 2.6 mM , (average forward velocity) 8.0 + 1.5 ml4 and (motility index) 8.5 C 2.1 mM. The effects of enalapril on forward velocity and on motility index appeared not to be reversible on washing. nowever, the percentage motility was restored by a 5-min wash to 6720.1% of control motility When ("=9, PcO.05) when prior incubation with enalapril had been 5 min. enalapril had been in contact with the spermatozoa for 60 min. a 5-min wash did not retore motility (7.5+_9.3% of control percentage motility, n=9, not significantly different from enalapril-treated suspensions). Enalapril 20 mM had no effect on viability (nigrosin-eosin stain technique) At 60 min the or hypoosmotic swelling, after either 5 or 60 min contact. viability of control suspensions was 66f4%, and of enalapril 20 mM suspensions was 68+5%. At 60 min the control samples contained 61f6% swollen spermatozoa and the enalapril 20 mM suspension contained 53+3% swollen spermatozoa ("=9, not significantly different). DISCUSSION This study demonstrates a concentration-related antimotility effect of the ACE inhibitor enalapril in washed human spermatozoa -in vitro. However, the potency ratio of the ACE inhibitors captopril and enalapril for reduction of motility of human spermatozoa is about 0.5 (7) and for inhibitors of ACE effect of enalapril is not about 0.1 (15). Thus, the sperm immobilization likely to be the result of inhibition of ACE, which has been shown to be present on spermatozoa (4,5). The ACE inhibitors block both forms of ACE, and also inhibit other dipeptidyl carboxypeptidases (16). Other actions of enalapril that could mediate its antimotility effect include reducing cyclic AMP concentration (17), reducing bradykinin levels (la), or increasing These effects would be expected to have a prostaglandin synthesis (19). deleterious effect on sperm function (20). Several drugs immobilize Since enalapril spermatozoa through stabilization of the cell membrane (21). Placzek is hydrophilic (22), it is unlikely to stabilize the sperm membrane. et al. (0) reported that neither enalapril nor captopril affects sperm OU?Z used were too low. motility, but in that study the concentrations results show that when the concentration of enalapril or captopril is increased slightly above the maximum used by Placzek et al., a clear antimotility effect is see". Of the semen parameters measured, enalapril is more specific than captopril At concentrations producing complete as a" inhibitor of sperm motility. abolition of forward velocity, enalapril did not impair membrane function or
FEBRUARY 1990VOL. 41 NO. 2
215
CONTRACEPTION
..
.
I.
! ! ,*
-!
-‘I
w,_ -;,“-
..&
:::
0 ( swh)
216
1113013A
XXNI
~11lIlCd
FEBRUARY 1990 VOL. 41 NO. 2
CONTRACEPTION
viability as judged by the hypoosmotic swelling test stain test. By contrast, captopril impairs membrane with loss of movement (7).
and the nigrosin-eosin function in parallel
A close relationship exists between sperm movement and fertility (23). Ejaculates with spermatozoa having low percentage motility (24), subnormal forward velocities (23) and low motility indices (25) are less likely to fertilize ova. The fact that these three vital parameters of motility were concomitantly impaired by enalapril makes it, or a derivative, worth investigating further as a vaginal contraceptive. Ideally, such a derivative should be, compared to enalapril, less easily reversed by washing in, for example, cervical fluid.
ACKNOWLEDGEMENTS Mr. G A S Premakumara
for
technical
assistance.
REFERENCES 1.
Jaiswal A, Joshi P, Kumar converting enzyme in the Andrologia 1984; 16:410-6.
M U, Panda J N, Singh L N. Angiotensin testes, and epididymis of mammals.
2.
Strittmatter S M, Snyder male reproductive system: captoprjl. Endocrinology
3.
Cushman D W, Cheung enzyme in tissues 250:261-5.
4.
Yotsumoto H, sat0 s, Shibuya M. Localization of angiotensin converting enzyme (dipeptidyl carboxypeptidase) in swine sperm by immunofluorescence. Life Sci 1984; 35:1257-61.
5.
Scandellari C. Foresta Indino Manoni C, M, F, human spermatozoa and its Angiotensin-converting enzyme content of release during capacitation. Fertil Steril 1987; 47:1000-3.
6.
Hohlbrugger G, Pschorr enzyme in the ejaculate Steril 1984; 41:324-5.
7.
Ratnasooriya effect of 16:935-6.
8.
ACE-inhihitors Placzek R, Krassnigg F, Schill W-B. Effect of and alpha calmodulin antagonists, acetycholine receptor blocking, Arch Anrdol receptor blocking agents on motility of human sperm. 1988; 21:1-10.
S H. Angiotensin-converting enzyme in !jhe Autoradiographic visualization with [ HI1984; 115:2332-41.
converting H S. Concentration of angiotensin 1971; of the rat. Biochem Biophys Acta
J, Dahlheim of fertile
W D, Rathnayaka captopril on human
FEBRUARY 1990 VOL. 41 NO. 2
M. Angiotensin and infertile
I
converting Fertil me".
inhibitory P C, Wadsworth R M. The Hed Sci Res 1988; sperm motility.
217
CONTRACEPTION
9.
Gomez H J, Cirillo, U J and Irui" J D. Enalapril: pharmacology. Drugs 1985; 30(1):13-24.
a review
of human
10. Beleey M A, Eliasson R, Gallegos A J et- al. (eds.). Laboratory MUCUS Manual for the Examination of Human Semen and Semen-Cervical Interaction. (WHO) Singapore: Press Concern, 1980; l-23. D G. The culture of mouse 11. Biggers J D, Whitten W K, Whittingham eggs in vitro. In: Daniel J C (ed.) Methods in mammalian embyology. San Francisco Freeman, 1971; 86. 12. Daunter B, biochemistry
Hill R, Hennessey 1. Andrologia 1981;
J, Mackay 13:131-41.
E
U. Seminal
plasma
13. Keel B A, Webster B W, Roberts D K. Effects of cryopreservation on human spermatozoa. the motility characteristics of J Reprod Fert 1987; 81:213-220. 14. Jeyendran R S, Van der Ven H H, Perez-Peloez M, Crabo B G, Zeneveld L J D. Development of an assay to assess the functional integrity of the human sperm membrane and its relationship to other semen characteristics. J Reprod Fert 1984; 70:219-28. 15. Laragh J H. Conceptual diagnostic and therapeutic dimensions of renin-system profiling of hypertensive disorders and of congestive heart failure: four new research frontiers. In: Doyle A E, Beam A G (eds.). Hypertension angiotensin system: Therapeutic and the approaches. New York: Raven Press, 1983; 44-76. 16. Soffer R L. Some thoughts' about inhibition of the angiotensin system. In: the Doyle A E, Bean A G (eds.). Hypertension and angiotensin system: Therapeutic New York: Raven Press, approaches. 1983:179-89. 17.
Geiger H, Bahner U, Heidland A. Effect of Palkouits M, angiotensin-converting enzyme inhibitors captopril and enalapril on CAMP content of specific brain areas in spontaneously hypertensive rats. Clin Expt Pharmac Physiol 1987; 14:327-32.
18. Schill W B, Haberland G L. Kinin-induced motility. Hoppe Seylers Physiol Chem 1974;
enhancement 325:229-31.
of
sperm
19. Zusman R M. Renin and non-renin-mediated antihypertensive actions Kidney Int 1984; 25:969-83. of converting enzyme inhibitors. 20. Lessing J B, Paz G F, Peyser M R, Homonnai 2 T, Brenner S H, Weiss G. Lxboratory efforts to improve motility of human sperm. Seminars Reprod Endocri" 1987; 5:91-E. Turner 21. Hong C Y, P. Influence of immobilizing effect of P-adrenoceptor Pharmacol 1982; 14:269-72.
218
lipid solubility on the sperm blocking drugs. Br J Clin
FEBRUARY 1990 VOL. 41 NO. 2
CONTRACEPTION
22. Patch&t In: Doyle A E, Bear-n A G A A. The design of enalapril. (eds.). Hypertension system: Therapeutic angiotensin and the approaches. New York: Raven Press, 1983:155-65. 23. Hartman H G. Correlation Steril 1965; 16:632-44. 24. Amelar R D, Dubin 1980; 34:197-215.
among
criteria
L, Schoenfeld
of
C. Sperm
25. Mathur S, Carlton M, Ziegler J, Rust P Fertil computerized sperm motion analysis.
FEBRUARY 1990 VOL. 41 NO. 2
semen
motility.
quality.
Fertil
Fertil
Steril
H 0. A F, Williamson Steril 1986; 46:484-88.
219