Central Autonomic Network Regions and Hypertension: Unveiling Sympathetic Activation and Genetic Therapeutic Perspectives
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Ethical Considerations
2.2. Animals
2.3. Metabolic Evaluation
2.4. Surgical procedures
2.4.1. Implantation of Radio-Telemetry Probes
2.4.2. Viral Vector Construction and Validation
2.4.3. Central Microinjection Sites
2.4.4. Cardiorespiratory Evaluation
2.5. Morphological Studies
2.6. Data Acquisition and Analysis
2.6.1. Baroreceptor, Chemoreceptor Reflex, and Overall Autonomic Tone Evaluation
- Baroreceptor Reflex Evaluation: The baroreceptor reflex gain (BRG) was quantified using the following formula: BRG = (HRbasal-HRBPmax)/(BPmax-BPbasal) (bpm mmHg −1). This calculation provides a measure of the baroreceptor reflex sensitivity, which is a key mechanism for short-term blood pressure regulation [23].
- Chemoreceptor Reflex Evaluation: The chemoreceptor reflex (ChR) was evaluated by measuring the change in the respiratory rate (∆ChR) in response to lobeline stimulation. The respiratory rate (RespR) was derived from the tracheal pressure before and after the lobeline administration. The following formula was used: ∆ChR = RespRlobeline-RespRbasal [24].
- Autonomic Tone Evaluation: To assess the overall autonomic tone, a spectral analysis of the systolic blood pressure (SBP) and RR interval data was performed. The low-frequency (LF) band (0.15–0.6 Hz) of the SBP was used as an indicator of the sympathetic activity, while the high-frequency (HF) band (0.6–2.0 Hz) of the RR interval was used as an indicator of the parasympathetic activity. The data were analysed in the frequency domain using a Fast Fourier Transform with the in-house software Fisiosinal [25].
- Respiratory Sinus Arrhythmia: Respiratory sinus arrhythmia, a measure of parasympathetic activity, was quantified as the ratio of the longer RR interval of the ECG during expiration to the shorter RR interval during inspiration, as described previously [26].
2.6.2. Circadian BP and HR Profile
2.7. Statistical Analysis
3. Results
3.1. Lateral Parabrachial Nucleus
3.1.1. LPBN Lentiviral Microinjection Influence on Long-Term Blood Pressure Control
3.1.2. LPBN Lentiviral Microinjection Impact on Sympathetic Tone
3.1.3. Blood Pressure and Heart Rate Circadian Variation
3.1.4. Parasympathetic Tonus Indirect Assessment
3.1.5. Cardiovascular Reflexes Evaluation
3.2. Periaqueductal Gray Matter
3.2.1. PAG Lentiviral Microinjection Influence on 24 h Mean Values of Blood Pressure and Heart Rate
3.2.2. PAG Lentiviral Microinjection Effect on Sympathetic Output
3.2.3. Blood Pressure and Heart Rate Circadian Variation
3.2.4. Indirect Quantification of Vagal Tonus
3.2.5. Cardiorespiratory Evaluation
3.3. Kolliker-Fuse Nucleus
3.3.1. KF Lentiviral Microinjection Influence on 24 h Mean Values of Blood Pressure and Heart Rate
3.3.2. Effect of KF LVV-hKir2.1 Microinjection on Sympathetic Output
3.3.3. Blood Pressure and Heart Rate Circadian Variation
3.3.4. Indirect Assessment of Vagal Tonus
3.3.5. Cardiorespiratory Reflex Assessment
4. Discussion
5. Limitations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Light Phase | Dark Phase | |||||||
---|---|---|---|---|---|---|---|---|
Group | sBP | dBP | mBP | HR | sBP | dBP | mBP | HR |
Basal conditions | ||||||||
PAG | 149 ± 2 | 126 ± 3 | 134 ± 3 | 309 ± 6 | 156 ± 3 | 133 ± 5 | 141 ± 4 | 343 ± 8 |
SHAM | 157 ± 5 | 130 ± 5 | 139 ± 5 | 289 ± 7 | 160 ± 5 | 133 ± 6 | 142 ± 6 | 316 ± 8 |
60 days after microinjection | ||||||||
PAG | 164 ± 2 *** | 140 ± 4 * | 148 ± 3 ** | 284 ± 4 *** | 172 ± 3 ** | 148 ± 7 | 156 ± 5 * | 322 ± 5 ** |
SHAM | 170 ± 12 | 141 ± 12 | 151 ± 11 | 268 ± 4 | 175 ± 11 | 147 ± 11 | 156 ± 11 | 311 ± 3 |
Light Phase | Dark Phase | |||||||
---|---|---|---|---|---|---|---|---|
Group | sBP | dBP | mBP | HR | sBP | dBP | mBP | HR |
Basal conditions | ||||||||
KF | 148 ± 2 | 127 ± 3 | 134 ± 3 | 322 ± 9 | 152 ± 5 | 131 ± 4 | 138 ± 4 | 353 ± 8 |
SHAM | 157 ± 5 | 131 ± 6 | 140 ± 5 | 295 ± 5 | 160 ± 5 | 134 ± 6 | 143 ± 6 | 321 ± 6 |
60 days after microinjection | ||||||||
KF | 161 ± 6 * | 138 ± 5 * | 146 ± 5 * | 294 ± 14 * | 166 ± 7 * | 142 ± 6 * | 150 ± 6 * | 327 ± 7 * |
SHAM | 177 ± 10 | 148 ± 12 | 158 ± 11 | 266 ± 5 | 181 ± 11 | 153 ± 13 | 163 ± 12 | 305 ± 8 |
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Geraldes, V.; Laranjo, S.; Nunes, C.; Rocha, I. Central Autonomic Network Regions and Hypertension: Unveiling Sympathetic Activation and Genetic Therapeutic Perspectives. Biology 2023, 12, 1153. https://doi.org/10.3390/biology12081153
Geraldes V, Laranjo S, Nunes C, Rocha I. Central Autonomic Network Regions and Hypertension: Unveiling Sympathetic Activation and Genetic Therapeutic Perspectives. Biology. 2023; 12(8):1153. https://doi.org/10.3390/biology12081153
Chicago/Turabian StyleGeraldes, Vera, Sérgio Laranjo, Catarina Nunes, and Isabel Rocha. 2023. "Central Autonomic Network Regions and Hypertension: Unveiling Sympathetic Activation and Genetic Therapeutic Perspectives" Biology 12, no. 8: 1153. https://doi.org/10.3390/biology12081153