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Neuronal nitric oxide synthase within paraventricular nucleus: blood pressure and baroreflex in two-kidney, one-clip hypertensive rats.
Exp Physiol. 2010 Aug; 95(8):845-57.EP

Abstract

The renin-angiotensin system is activated in the early phase of two-kidney, one-clip (2K-1C) hypertension. The paraventricular nucleus (PVN) integrates inputs regulating sympathetic outflow. The PVN receives inputs from plasma angiotensin II via projections from circumventricular organs and from renal afferent nerves transmitted via the nucleus tractus solitarii. Nitric oxide within the PVN may exert a sympathoinhibitory effect. These studies tested whether decreasing endogenous nitric oxide by introducing dominant negative (DN) constructs for neuronal nitric oxide synthase (nNOS) into PVN chronically augments hypertension and/or modulates baroreflex function. Male 6-week-old Sprague-Dawley rats underwent sham surgery or right renal artery clipping and placement of radiotelemetry transmitters. One week later, the PVN was injected bilaterally with 250 nl artificial cerebrospinal fluid containing 250 ng microl(-1) of RSV beta-galactosidase (beta-Gal), cytomegalovirus (CMV) wild-type (WT nNOS), or respiratory syncytial virus (RSV) haeme domain or RSV haemeRedF (DN nNOS). Haemodynamics were monitored for 5 weeks. Then left renal nerve electrodes were placed, and 2 days later the rats underwent baroreflex testing in the conscious state. The rise in mean arterial pressure (MAP) was significantly potentiated in the DN nNOS 2K-1C group beyond 15 days after PVN injection. By day 35, MAP in the 2K-1C groups was 152 +/- 6.3 (beta-Gal), 155.1 +/- 6.6 (WT nNOS) and 179 +/- 5.4 mmHg (DN nNOS; P < 0.01 versus all other groups). Sham-clipped rats remained normotensive. All groups displayed progressive bradycardia over time that was attenuated in the DN nNOS 2K-1C group. Baroreflex curves shifted to higher pressures, and baroreflex sensitivity of heart rate was diminished to a similar extent in all groups of 2K-1C rats. The baroreflex response of renal sympathetic nerve activity was preserved. The PVN tissue from DN nNOS rats had decreased dimerization of nNOS and generation of total nitric oxide. These findings indicate that chronic interference of nNOS dimerization required for generation of nitric oxide within the PVN potentiates the increase of blood pressure by modulating the sympathoexcitation that accompanies renovascular hypertension.

Authors+Show Affiliations

Department of Internal Medicine, Wayne State University School of Medicine, 4160 John R. Street, no. 908, Detroit, MI 48201, USA. nrossi@med.wayne.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20494920

Citation

Rossi, Noreen F., et al. "Neuronal Nitric Oxide Synthase Within Paraventricular Nucleus: Blood Pressure and Baroreflex in Two-kidney, One-clip Hypertensive Rats." Experimental Physiology, vol. 95, no. 8, 2010, pp. 845-57.
Rossi NF, Maliszewska-Scislo M, Chen H, et al. Neuronal nitric oxide synthase within paraventricular nucleus: blood pressure and baroreflex in two-kidney, one-clip hypertensive rats. Exp Physiol. 2010;95(8):845-57.
Rossi, N. F., Maliszewska-Scislo, M., Chen, H., Black, S. M., Sharma, S., Ravikov, R., & Augustyniak, R. A. (2010). Neuronal nitric oxide synthase within paraventricular nucleus: blood pressure and baroreflex in two-kidney, one-clip hypertensive rats. Experimental Physiology, 95(8), 845-57. https://doi.org/10.1113/expphysiol.2009.051789
Rossi NF, et al. Neuronal Nitric Oxide Synthase Within Paraventricular Nucleus: Blood Pressure and Baroreflex in Two-kidney, One-clip Hypertensive Rats. Exp Physiol. 2010;95(8):845-57. PubMed PMID: 20494920.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuronal nitric oxide synthase within paraventricular nucleus: blood pressure and baroreflex in two-kidney, one-clip hypertensive rats. AU - Rossi,Noreen F, AU - Maliszewska-Scislo,Maria, AU - Chen,Haiping, AU - Black,Stephen M, AU - Sharma,Shruti, AU - Ravikov,Ruslan, AU - Augustyniak,Robert A, Y1 - 2010/05/21/ PY - 2010/5/25/entrez PY - 2010/5/25/pubmed PY - 2010/10/21/medline SP - 845 EP - 57 JF - Experimental physiology JO - Exp Physiol VL - 95 IS - 8 N2 - The renin-angiotensin system is activated in the early phase of two-kidney, one-clip (2K-1C) hypertension. The paraventricular nucleus (PVN) integrates inputs regulating sympathetic outflow. The PVN receives inputs from plasma angiotensin II via projections from circumventricular organs and from renal afferent nerves transmitted via the nucleus tractus solitarii. Nitric oxide within the PVN may exert a sympathoinhibitory effect. These studies tested whether decreasing endogenous nitric oxide by introducing dominant negative (DN) constructs for neuronal nitric oxide synthase (nNOS) into PVN chronically augments hypertension and/or modulates baroreflex function. Male 6-week-old Sprague-Dawley rats underwent sham surgery or right renal artery clipping and placement of radiotelemetry transmitters. One week later, the PVN was injected bilaterally with 250 nl artificial cerebrospinal fluid containing 250 ng microl(-1) of RSV beta-galactosidase (beta-Gal), cytomegalovirus (CMV) wild-type (WT nNOS), or respiratory syncytial virus (RSV) haeme domain or RSV haemeRedF (DN nNOS). Haemodynamics were monitored for 5 weeks. Then left renal nerve electrodes were placed, and 2 days later the rats underwent baroreflex testing in the conscious state. The rise in mean arterial pressure (MAP) was significantly potentiated in the DN nNOS 2K-1C group beyond 15 days after PVN injection. By day 35, MAP in the 2K-1C groups was 152 +/- 6.3 (beta-Gal), 155.1 +/- 6.6 (WT nNOS) and 179 +/- 5.4 mmHg (DN nNOS; P < 0.01 versus all other groups). Sham-clipped rats remained normotensive. All groups displayed progressive bradycardia over time that was attenuated in the DN nNOS 2K-1C group. Baroreflex curves shifted to higher pressures, and baroreflex sensitivity of heart rate was diminished to a similar extent in all groups of 2K-1C rats. The baroreflex response of renal sympathetic nerve activity was preserved. The PVN tissue from DN nNOS rats had decreased dimerization of nNOS and generation of total nitric oxide. These findings indicate that chronic interference of nNOS dimerization required for generation of nitric oxide within the PVN potentiates the increase of blood pressure by modulating the sympathoexcitation that accompanies renovascular hypertension. SN - 1469-445X UR - https://www.unboundmedicine.com/medline/citation/20494920/Neuronal_nitric_oxide_synthase_within_paraventricular_nucleus:_blood_pressure_and_baroreflex_in_two_kidney_one_clip_hypertensive_rats_ L2 - https://doi.org/10.1113/expphysiol.2009.051789 DB - PRIME DP - Unbound Medicine ER -