{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:19:12Z","timestamp":1785507552776,"version":"3.56.0"},"reference-count":70,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"AHA Strategically Focused Research Network on CKMS"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 DK129227"],"award-info":[{"award-number":["R01 DK129227"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Transformational Project Award from AHA","award":["CDA 25CDA1449142"],"award-info":[{"award-number":["CDA 25CDA1449142"]}]},{"name":"Transformational Project Award from AHA","award":["AHA"],"award-info":[{"award-number":["AHA"]}]},{"name":"AHA Predoctoral Fellowship","award":["25PRE1372769"],"award-info":[{"award-number":["25PRE1372769"]}]},{"name":"Dialysis Clinic, Inc. Paul Teschan Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inflammation is one of the mechanisms of renal disease development in salt-sensitive hypertension (SS-HTN). We have previously shown that Dahl SS rats exhibit higher renal histamine levels when fed a high-salt diet and reported that renal epithelium has abundant histaminergic system components. We hypothesized here that inhibition of histamine N-methyltransferase (HNMT) attenuates the development of hypertension and reduces renal damage in the Dahl SS rat.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Dahl SS rats implanted with telemeters were administered HNMT inhibitor SKF-91488 (3.0 mg\/kg\/day) or vehicle s.c., while fed a 4.0% NaCl high-salt diet for 21 days. Renal function and biometric parameters were assessed at endpoint; tissues were collected and subjected to IHC and Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We report attenuation of hypertension in the SKF-91488-treated group at endpoint (mean arterial pressure\u2009=\u2009132.6\u202f\u00b1\u202f11.8 vs 160.3\u202f\u00b1\u202f6.5 mm\u00a0Hg in control, P\u2009&amp;lt;\u2009.05) and proximal tubule damage measured with KIM-1 (0.8\u2009\u00b1\u20090.1 vs 1.7\u2009\u00b1\u20090.2% stained area fraction, P\u2009&amp;lt;\u2009.01). \u03b1SMA IHC of coronary vasculature in the SKF-91488 group demonstrated smaller vessel wall thickness relative to total diameter (P\u2009=\u2009.046). Renal abundance of histamine receptors 1 and 4 (P\u2009=\u2009.01\/both) and the pan-macrophage marker CD68 (P\u2009=\u2009.04) were higher in the renal cortex of the SKF-91488-treated group. Urinary Cl\u2212 excretion was higher in the SKF-91488-treated rats at the endpoint compared to vehicle controls (P\u2009&amp;lt;\u2009.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study demonstrated that HNMT inhibition alleviates blood pressure and proximal tubule damage in SS-HTN, potentially through immune-related mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajh\/hpag089","type":"journal-article","created":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T11:33:49Z","timestamp":1784460829000},"source":"Crossref","is-referenced-by-count":0,"title":["Histamine N-methyltransferase inhibition attenuates hypertension and proximal tubule damage in Dahl salt-sensitive rats fed a high-salt 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