{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:54:42Z","timestamp":1789977282082,"version":"4.0.1"},"reference-count":33,"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":[[1998,11]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014The role of neural nitric oxide synthase (nNOS) in regulating blood pressure (BP) remains uncertain. Recently it was reported that in mice lacking functional endothelial NOS (eNOS) genes (\u2212\/\u2212), acute administration of a nonselective NOS inhibitor,\n            <jats:italic>N<\/jats:italic>\n            <jats:sup>w<\/jats:sup>\n            -nitro-\n            <jats:sc>l<\/jats:sc>\n            -arginine, decreased mean BP, suggesting that NO released by non-eNOS isoforms increases BP. Because the inducible NOS isoform is not constitutively expressed and when induced causes hypotension, we hypothesize that it is NO produced by nNOS that increases BP in the absence of eNOS activity. To test this hypothesis, we studied the acute effect of selective and nonselective nNOS inhibitors on BP and cerebellar NOS activity in eNOS (\u2212\/\u2212), wild-type (+\/+), and heterozygous (+\/\u2212) mice as well as in +\/+ mice with renovascular hypertension. Because it is not known whether the decrease in BP caused by acute NOS inhibition in \u2212\/\u2212 mice can occur chronically, we also studied the effect of chronic NOS inhibition on both BP and cerebellar NOS activity. eNOS (\u2212\/\u2212) mice had higher BP than +\/+ or +\/\u2212mice, and acute administration of the selective nNOS inhibitor 7-nitroindazole (7-NI) decreased their mean BP from 137\u00b113 to 124\u00b112 mm Hg (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01). In +\/+, +\/\u2212, or renovascular hypertensive +\/+ mice, 7-NI caused a small but insignificant rise from 105\u00b15 to 110\u00b16 mm Hg, from 115\u00b19 to 119\u00b113 mm Hg, and from 146\u00b16 to 150\u00b16 mm Hg, respectively. Fifteen minutes after administration of 7-NI, cerebellar NOS activity decreased by 70%; however, this inhibitory effect was brief, since 2 hours after 7-NI administration NOS returned toward control values. Chronic oral or intraperitoneal administration of 7-NI did not inhibit cerebellar NOS activity, whereas the nonselective NOS inhibitor\n            <jats:italic>N<\/jats:italic>\n            <jats:sup>G<\/jats:sup>\n            -nitro-\n            <jats:sc>l<\/jats:sc>\n            -arginine methyl ester (L-NAME) decreased this activity by 50%. Therefore, we studied the effect of chronic L-NAME administration (4 weeks) on BP. In \u2212\/\u2212 mice, chronic L-NAME administration decreased BP from 135\u00b14 to 120\u00b13 mm Hg (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05), whereas in +\/+ and +\/\u2212mice, as expected, it increased BP from 109\u00b12 to 125\u00b13 mm Hg (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001) and from 107\u00b16 to 119\u00b15 mm Hg (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.02), respectively. After L-NAME administration was stopped, BP returned to baseline. These results suggest that in eNOS \u2212\/\u2212 mice, NO derived from nNOS increases BP both acutely and chronically.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.32.5.856","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"856-861","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":83,"title":["Role of nNOS in Blood Pressure Regulation in eNOS Null Mutant Mice"],"prefix":"10.1161","volume":"32","author":[{"given":"Nobutaka","family":"Kurihara","sequence":"first","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos E.","family":"Alfie","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Sigmon","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour-Eddine","family":"Rhaleb","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward G.","family":"Shesely","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar A.","family":"Carretero","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/288373a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.9.3375"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.57.030195.004011"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.23.6.1121"},{"key":"e_1_3_2_5_2","first-page":"10","volume":"14","year":"1993","unstructured":"F\u00f6rstermann U, Nakane M, Tracey WR, Pollock JS. 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Effects of NO on baroreflex control of heart rate and renal nerve activity in conscious rabbits. Am J Physiol. 1996;270:R1361\u2013R1370.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.24.4.439"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/345346a0"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12137.x"},{"key":"e_1_3_2_32_2","first-page":"999","volume":"2","year":"1994","unstructured":"Zagvazdin Y, Sancesario G, Fitzgerald MEC, Reiner A. The effect of 7-nitroindazole, an inhibitor of brain nitric oxide synthase (NOS), on basal cortical blood flow and on vasodilation induced by whisker stimulation. Abstr Soc Neurosci. 1994;2:999. Abstract.","journal-title":"Abstr Soc Neurosci"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(95)00254-4"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.32.5.856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T17:28:31Z","timestamp":1715534911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.32.5.856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,11]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1998,11]]}},"alternative-id":["10.1161\/01.HYP.32.5.856"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.32.5.856","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,11]]},"assertion":[{"value":"1998-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-07-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}