{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T23:04:25Z","timestamp":1774566265951,"version":"3.50.1"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2002,11]]},"abstract":"<jats:p>\n            Sildenafil inhibits cGMP breakdown by phosphodiesterase 5. In vitro, increased cGMP levels inhibit cAMP breakdown by phosphodiesterase 3. It is uncertain, however, whether sildenafil increases biological effects of interventions increasing cAMP levels in vivo. The objective of the present study in 40 healthy male volunteers was to determine the existence and extent of interactions with sildenafil and vasodilators acting via cGMP or cAMP or independently from these mediators on the arterial tone of the human forearm. Forearm blood flow (FBF) responses (plethysmography) to brachial artery infusions of 3 doses each of nitroglycerin, which increases cGMP levels; of isoprenaline and milrinone, which increase cAMP levels; and of verapamil as a control were assessed at baseline and 80 minutes after 50 mg oral sildenafil in 10 volunteers each. Sildenafil increased FBF (2.5\u00b10.1 to 3.5\u00b10.2 mL\/min per 100 mL,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001; n=40). At equipotent vasodilator dosages, sildenafil increased FBF from 7.5\u00b11.0 to 9.8\u00b11.2 mL\/min per 100 mL for nitroglycerin, from 8.3\u00b11.0 to 10.4\u00b11.4 mL\/min per 100 mL for isoprenaline, and from 8.1\u00b11.0 to 10.3\u00b11.2 mL\/min per 100 mL for milrinone and slightly decreased FBF from 7.7\u00b11.3 to 7.1\u00b11.2 mL\/min per 100 mL for verapamil. ANOVA for repeated measures revealed a significant interaction between sildenafil and the type of vasodilator on FBF (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01). The responses of FBF to nitroglycerin, milrinone, and isoprenaline after sildenafil were similarly increased compared with the response to verapamil (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01). Sildenafil markedly enhanced the arterial vasodilator response to nitroglycerin, milrinone, and isoprenaline. The response to milrinone and isoprenaline is compatible with an interaction between cGMP and phosphodiesterase 3 or an enhancement of the NO component of cAMP-mediated vasodilation, and raises the possibility of enhanced biological effects of interventions leading to increases of cAMP in the presence of sildenafil.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.0000036027.71527.3e","type":"journal-article","created":{"date-parts":[[2002,10,31]],"date-time":"2002-10-31T22:49:12Z","timestamp":1036104552000},"page":"763-767","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Interaction of Sildenafil With cAMP-Mediated Vasodilation In Vivo"],"prefix":"10.1161","volume":"40","author":[{"given":"Christoph","family":"Schalcher","sequence":"first","affiliation":[{"name":"From the Division of Cardiology, Department of Internal Medicine, University Hospital (C. Schalcher, K.S., H.P.B.-L., R.S., E.O., C. Scharf, G.S., W.K.), Zu\u0308rich, Switzerland; and Triemli Hospital (O.B.), Zu\u0308rich, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Schad","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Internal Medicine, University Hospital (C. Schalcher, K.S., H.P.B.-L., R.S., E.O., C. Scharf, G.S., W.K.), Zu\u0308rich, Switzerland; and Triemli Hospital (O.B.), Zu\u0308rich, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans Peter","family":"Brunner-La Rocca","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Internal Medicine, University Hospital (C. Schalcher, K.S., H.P.B.-L., R.S., E.O., C. Scharf, G.S., W.K.), Zu\u0308rich, Switzerland; and Triemli Hospital (O.B.), Zu\u0308rich, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Schindler","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Internal Medicine, University Hospital (C. Schalcher, K.S., H.P.B.-L., R.S., E.O., C. Scharf, G.S., W.K.), Zu\u0308rich, Switzerland; and Triemli Hospital (O.B.), Zu\u0308rich, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwin","family":"Oechslin","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Internal Medicine, University Hospital (C. Schalcher, K.S., H.P.B.-L., R.S., E.O., C. Scharf, G.S., W.K.), Zu\u0308rich, Switzerland; and Triemli Hospital (O.B.), Zu\u0308rich, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Scharf","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Internal Medicine, University Hospital (C. Schalcher, K.S., H.P.B.-L., R.S., E.O., C. Scharf, G.S., W.K.), Zu\u0308rich, Switzerland; and Triemli Hospital (O.B.), Zu\u0308rich, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabor","family":"Suetsch","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Internal Medicine, University Hospital (C. Schalcher, K.S., H.P.B.-L., R.S., E.O., C. Scharf, G.S., W.K.), Zu\u0308rich, Switzerland; and Triemli Hospital (O.B.), Zu\u0308rich, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osmund","family":"Bertel","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Internal Medicine, University Hospital (C. Schalcher, K.S., H.P.B.-L., R.S., E.O., C. Scharf, G.S., W.K.), Zu\u0308rich, Switzerland; and Triemli Hospital (O.B.), Zu\u0308rich, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Kiowski","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Internal Medicine, University Hospital (C. Schalcher, K.S., H.P.B.-L., R.S., E.O., C. Scharf, G.S., W.K.), Zu\u0308rich, Switzerland; and Triemli Hospital (O.B.), Zu\u0308rich, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1992.tb00433.x"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199201093260203"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.1998.00553.x"},{"key":"e_1_3_2_4_2","first-page":"47","volume":"8","year":"1996","unstructured":"Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C. Sildenafil: an orally active type 5 cyclic GMP\u2013specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996; 8: 47\u201352.","journal-title":"Int J Impot Res"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.56.1.124"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)63299-3"},{"key":"e_1_3_2_7_2","first-page":"309","volume":"62","year":"1998","unstructured":"Moreland RB, Goldstein I, Traish A. Sildenafil: a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells. Life Sci. 1998; 62: 309\u2013318.","journal-title":"Life Sci"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199805143382001"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.20.13729"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(98)00643-8"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1995.75.4.725"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00042-9"},{"key":"e_1_3_2_13_2","first-page":"3","volume":"102","year":"1999","unstructured":"Osterloh IH, Collins M, Wicker P, Wagner G. Sildenafil citrate (Viagra): overall safety profile in 18 double-blind, placebo controlled, clinical trials. Int J Clin Pract. 1999; 102 (suppl): 3\u20135.","journal-title":"Int J Clin Pract"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00045-4"},{"key":"e_1_3_2_15_2","first-page":"590","volume":"283","year":"2000","unstructured":"Mitka M. Some men who take Viagra die: why? JAMA. 2000; 283: 590\u2013593.","journal-title":"JAMA"},{"key":"e_1_3_2_16_2","first-page":"553A.","volume":"35","year":"2000","unstructured":"Azarbal B, Mirocha J, Shah PK, Cercek B, Kaul S. Adverse cardiovascular events associated with the use of Viagra. J Am Coll Cardiol. 2000; 35 (suppl 2): 553A. Abstract.","journal-title":"J Am Coll Cardiol"},{"key":"e_1_3_2_17_2","first-page":"I-637.","volume":"98","year":"1998","unstructured":"Webb DJ, Boolell M, Muirhead DC. Cardiovascular effects of phosphodiesterase type 5 inhibition with concomitant nitrate therapy. Circulation. 1998; 98 (suppl I): I-637. Abstract.","journal-title":"Circulation"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.65.6.301"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.11.6823"},{"key":"e_1_3_2_20_2","first-page":"639","volume":"50","year":"1999","unstructured":"Lugnier C, Keravis T, Eckly-Michel A. Cross talk between NO and cyclic nucleotide phosphodiesterases in the modulation of signal transduction in blood vessel. J Physiol Pharmacol. 1999; 50: 639\u2013652.","journal-title":"J Physiol Pharmacol"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0960439"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.25.5.918"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(98)00776-0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410X.1997.00206.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(99)00371-4"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200006013422201"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00252-X"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.84.2.186"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00043-0"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14507.x"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.30.4.918"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.95.9.2293"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119732"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199611000-00022"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.25.3068"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00046-6"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.0000036027.71527.3E","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T16:52:53Z","timestamp":1715532773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.0000036027.71527.3E"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,11]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2002,11]]}},"alternative-id":["10.1161\/01.HYP.0000036027.71527.3E"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.0000036027.71527.3e","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,11]]},"assertion":[{"value":"2002-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-08-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-09-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}