Vera Geraldes1, Nataniel Goncalves-Rosa1, Beihui Liu2, Julian F R Paton2, Isabel Rocha3. 1. Faculty of Medicine & Centro de Cardiologia of University of Lisbon, Portugal. 2. School of Physiology & Pharmacology, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK. 3. Faculty of Medicine & Centro de Cardiologia of University of Lisbon, Portugal. Electronic address: Isabelrocha@fm.ul.pt.
Abstract
BACKGROUND: It is well established that sympathetic nervous system is responsible for the onset, development and maintenance of neurogenic hypertension. The rostroventrolateral medulla (RVLM) and medullo-cervical pressor area (MCPA) are important central sympathoexcitatory regions whose role on neurogenic hypertension remains unknown. OBJECTIVE: To establish RVLM and MCPA roles in the long-term regulation of blood pressure by depressing their neuron activity through the over-expression of hKir2.1-potassium channel in conscious spontaneously hypertensive rats (SHR). METHODS: In SHR, a lentiviral vector LVV-hKir2.1 was microinjected into RVLM or MCPA areas. A sham group was injected with LVV-eGFP. Blood pressure (BP) and heart rate (HR) were continuously monitored for 75 days. Baroreflex and chemoreflex functions were evaluated. Baroreflex gain, chemoreflex sensitivity, BP and HR variability were calculated. RESULTS: LVV-hKir2.1 expression in RVLM, but not in MCPA, produced a significant time-dependent decrease in systolic, diastolic, mean-BP and LF of systolic BP at 60-days post-injection. No significant changes were seen in LVV-eGFP RVLM injected SHR. CONCLUSION: Data show that chronic expression of Kir2.1 in the RVLM of conscious SHR caused a marked and sustained decrease in BP without changes in the baro- and peripheral chemoreceptor reflex evoked responses. This decrease was mostly due to a reduction in sympathetic output revealed indirectly by a decrease in the power density of the SBP-LF band. Our data are amongst the firsts to demonstrate the role of the RVLM in maintaining BP levels in hypertension in conscious SHR. We suggest that a decrease in RVLM neuronal activity is an effective anti-hypertensive treatment strategy.
BACKGROUND: It is well established that sympathetic nervous system is responsible for the onset, development and maintenance of neurogenic hypertension. The rostroventrolateral medulla (RVLM) and medullo-cervical pressor area (MCPA) are important central sympathoexcitatory regions whose role on neurogenic hypertension remains unknown. OBJECTIVE: To establish RVLM and MCPA roles in the long-term regulation of blood pressure by depressing their neuron activity through the over-expression of hKir2.1-potassium channel in conscious spontaneously hypertensive rats (SHR). METHODS: In SHR, a lentiviral vector LVV-hKir2.1 was microinjected into RVLM or MCPA areas. A sham group was injected with LVV-eGFP. Blood pressure (BP) and heart rate (HR) were continuously monitored for 75 days. Baroreflex and chemoreflex functions were evaluated. Baroreflex gain, chemoreflex sensitivity, BP and HR variability were calculated. RESULTS: LVV-hKir2.1 expression in RVLM, but not in MCPA, produced a significant time-dependent decrease in systolic, diastolic, mean-BP and LF of systolic BP at 60-days post-injection. No significant changes were seen in LVV-eGFP RVLM injected SHR. CONCLUSION: Data show that chronic expression of Kir2.1 in the RVLM of conscious SHR caused a marked and sustained decrease in BP without changes in the baro- and peripheral chemoreceptor reflex evoked responses. This decrease was mostly due to a reduction in sympathetic output revealed indirectly by a decrease in the power density of the SBP-LF band. Our data are amongst the firsts to demonstrate the role of the RVLM in maintaining BP levels in hypertension in conscious SHR. We suggest that a decrease in RVLM neuronal activity is an effective anti-hypertensive treatment strategy.
Authors: Patrice G Guyenet; Ruth L Stornetta; George M P R Souza; Stephen B G Abbott; Virginia L Brooks Journal: Hypertension Date: 2020-06-29 Impact factor: 10.190
Authors: Ian C Wenker; Chikara Abe; Kenneth E Viar; Daniel S Stornetta; Ruth L Stornetta; Patrice G Guyenet Journal: J Neurosci Date: 2017-03-31 Impact factor: 6.167
Authors: Tao Yang; Victor Aquino; Gilberto O Lobaton; Hongbao Li; Luis Colon-Perez; Ruby Goel; Yanfei Qi; Jasenka Zubcevic; Marcelo Febo; Elaine M Richards; Carl J Pepine; Mohan K Raizada Journal: J Am Heart Assoc Date: 2019-02-19 Impact factor: 5.501