{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T07:05:05Z","timestamp":1770534305519,"version":"3.49.0"},"reference-count":66,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,19]],"date-time":"2018-01-19T00:00:00Z","timestamp":1516320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/12\/6\/29670"],"award-info":[{"award-number":["RG\/12\/6\/29670"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Does chronic reduction of neuronally generated nitric oxide in the hypothalamic paraventricular nucleus affect the set\u2010point regulation of blood pressure and sympathetic activity destined to the kidneys?<\/jats:p>\n<\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Within the hypothalamic paraventricular nucleus, nitric oxide generated by neuronal nitric oxide synthase plays a major constitutive role in suppressing long term the levels of both ongoing renal sympathetic activity and arterial pressure in conscious Wistar rats. This finding unequivocally demonstrates a mechanism by which the diencephalon exerts a tonic influence on sympathetic discharge to the kidney and may provide the basis for both blood volume and osmolality homeostasis.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in cardiovascular and neuroendocrine regulation. Application of nitric oxide donors to the PVN stimulates GABAergic transmission, and may suppress sympathetic nerve activity (SNA) to lower arterial pressure. However, the role of endogenous nitric oxide within the PVN in regulating renal SNA chronically remains to be established in conscious animals. To address this, we used our previously established lentiviral vectors to knock down neuronal nitric oxide synthase (nNOS) selectively in the PVN of conscious Wistar rats. Blood pressure and renal SNA were monitored simultaneously and continuously for 21\u00a0days (<jats:italic>n<\/jats:italic>\u00a0=\u00a014) using radio\u2010telemetry. Renal SNA was normalized to maximal evoked discharge and expressed as a percentage change from baseline. The PVN was microinjected bilaterally with a neurone\u2010specific tetracycline\u2010controllable lentiviral vector, expressing a short hairpin miRNA30 interference system targeting nNOS (<jats:italic>n<\/jats:italic>\u00a0=\u00a07) or expressing a mis\u2010sense as control (<jats:italic>n<\/jats:italic>\u00a0=\u00a07). Recordings continued for a further 18\u00a0days. The vectors also expressed green fluorescent protein, and successful expression in the PVN and nNOS knockdown were confirmed histologically <jats:italic>post hoc<\/jats:italic>. Knockdown of nNOS expression in the PVN resulted in a sustained increase in blood pressure (from 95\u00a0\u00b1\u00a02 to 104\u00a0\u00b1\u00a03\u00a0mmHg, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), with robust concurrent sustained activation of renal SNA (&gt;70%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). The study reveals a major role for nNOS\u2010derived nitric oxide within the PVN in chronic set\u2010point regulation of cardiovascular autonomic activity in the conscious, normotensive rat.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep086744","type":"journal-article","created":{"date-parts":[[2017,12,7]],"date-time":"2017-12-07T14:23:01Z","timestamp":1512656581000},"page":"419-428","source":"Crossref","is-referenced-by-count":16,"title":["Hypothalamic paraventricular nucleus neuronal nitric oxide synthase activity is a major determinant of renal sympathetic discharge in conscious Wistar rats"],"prefix":"10.1113","volume":"103","author":[{"given":"F. 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V.","family":"Roloff","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Kasparov","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7410-2913","authenticated-orcid":false,"given":"J. F. 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