Role of Mineralocorticoid and Angiotensin Type 1 Receptors in the Paraventricular Nucleus in Angiotensin-Induced Hypertension
The hypothalamic paraventricular nucleus (PVN) is an important site where an interaction between circulating angiotensin (Ang) and mineralocorticoid receptor (MR) activity may modify sympathetic nerve activity (SNA) to influence long-term elevation of blood pressure. We examined in conscious Ang II-...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-03-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.640373/full |
| _version_ | 1818948461803864064 |
|---|---|
| author | Sandra L. Burke Benjamin Barzel Kristy L. Jackson Cindy Gueguen Morag J. Young Geoffrey A. Head Geoffrey A. Head |
| author_facet | Sandra L. Burke Benjamin Barzel Kristy L. Jackson Cindy Gueguen Morag J. Young Geoffrey A. Head Geoffrey A. Head |
| author_sort | Sandra L. Burke |
| collection | DOAJ |
| description | The hypothalamic paraventricular nucleus (PVN) is an important site where an interaction between circulating angiotensin (Ang) and mineralocorticoid receptor (MR) activity may modify sympathetic nerve activity (SNA) to influence long-term elevation of blood pressure. We examined in conscious Ang II-treated rabbits, the effects on blood pressure and tonic and reflex renal SNA (RSNA) of microinjecting into the PVN either RU28318 to block MR, losartan to block Ang (AT1) receptors or muscimol to inhibit GABAA receptor agonist actions. Male rabbits received a moderate dose of Ang II (24 ng/kg/min subcutaneously) for 3 months (n = 13) or sham treatment (n = 13). At 3 months, blood pressure increased by +19% in the Ang II group compared to 10% in the sham (P = 0.022) but RSNA was similar. RU28318 lowered blood pressure in both Ang II and shams but had a greater effect on RSNA and heart rate in the Ang II-treated group (P < 0.05). Losartan also lowered RSNA, while muscimol produced sympatho-excitation in both groups. In Ang II-treated rabbits, RU28318 attenuated the blood pressure increase following chemoreceptor stimulation but did not affect responses to air jet stress. In contrast losartan and muscimol reduced blood pressure and RSNA responses to both hypoxia and air jet. While neither RU28318 nor losartan changed the RSNA baroreflex, RU28318 augmented the range of the heart rate baroreflex by 10% in Ang II-treated rabbits. Muscimol, however, augmented the RSNA baroreflex by 11% in sham animals and none of the treatments altered baroreflex sensitivity. In conclusion, 3 months of moderate Ang II treatment promotes activation of reflex RSNA principally via MR activation in the PVN, rather than via activation of AT1 receptors. However, the onset of hypertension is independent of both. Interestingly, the sympatho-excitatory effects of muscimol in both groups suggest that overall, the PVN regulates a tonic sympatho-inhibitory influence on blood pressure control. |
| first_indexed | 2024-12-20T08:47:10Z |
| format | Article |
| id | doaj.art-c4e2bad8926a47b6a97b4c7c441c76b2 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-20T08:47:10Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-c4e2bad8926a47b6a97b4c7c441c76b22022-12-21T19:46:14ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-03-011210.3389/fphys.2021.640373640373Role of Mineralocorticoid and Angiotensin Type 1 Receptors in the Paraventricular Nucleus in Angiotensin-Induced HypertensionSandra L. Burke0Benjamin Barzel1Kristy L. Jackson2Cindy Gueguen3Morag J. Young4Geoffrey A. Head5Geoffrey A. Head6Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, AustraliaNeuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, AustraliaNeuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, AustraliaNeuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, AustraliaCardiovascular Endocrinology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, AustraliaNeuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, AustraliaDepartment of Pharmacology, Monash University, Clayton, VIC, AustraliaThe hypothalamic paraventricular nucleus (PVN) is an important site where an interaction between circulating angiotensin (Ang) and mineralocorticoid receptor (MR) activity may modify sympathetic nerve activity (SNA) to influence long-term elevation of blood pressure. We examined in conscious Ang II-treated rabbits, the effects on blood pressure and tonic and reflex renal SNA (RSNA) of microinjecting into the PVN either RU28318 to block MR, losartan to block Ang (AT1) receptors or muscimol to inhibit GABAA receptor agonist actions. Male rabbits received a moderate dose of Ang II (24 ng/kg/min subcutaneously) for 3 months (n = 13) or sham treatment (n = 13). At 3 months, blood pressure increased by +19% in the Ang II group compared to 10% in the sham (P = 0.022) but RSNA was similar. RU28318 lowered blood pressure in both Ang II and shams but had a greater effect on RSNA and heart rate in the Ang II-treated group (P < 0.05). Losartan also lowered RSNA, while muscimol produced sympatho-excitation in both groups. In Ang II-treated rabbits, RU28318 attenuated the blood pressure increase following chemoreceptor stimulation but did not affect responses to air jet stress. In contrast losartan and muscimol reduced blood pressure and RSNA responses to both hypoxia and air jet. While neither RU28318 nor losartan changed the RSNA baroreflex, RU28318 augmented the range of the heart rate baroreflex by 10% in Ang II-treated rabbits. Muscimol, however, augmented the RSNA baroreflex by 11% in sham animals and none of the treatments altered baroreflex sensitivity. In conclusion, 3 months of moderate Ang II treatment promotes activation of reflex RSNA principally via MR activation in the PVN, rather than via activation of AT1 receptors. However, the onset of hypertension is independent of both. Interestingly, the sympatho-excitatory effects of muscimol in both groups suggest that overall, the PVN regulates a tonic sympatho-inhibitory influence on blood pressure control.https://www.frontiersin.org/articles/10.3389/fphys.2021.640373/fullhypertensionsympathetic nerve activityangiotensin IIaldosteroneRU28318rabbit |
| spellingShingle | Sandra L. Burke Benjamin Barzel Kristy L. Jackson Cindy Gueguen Morag J. Young Geoffrey A. Head Geoffrey A. Head Role of Mineralocorticoid and Angiotensin Type 1 Receptors in the Paraventricular Nucleus in Angiotensin-Induced Hypertension Frontiers in Physiology hypertension sympathetic nerve activity angiotensin II aldosterone RU28318 rabbit |
| title | Role of Mineralocorticoid and Angiotensin Type 1 Receptors in the Paraventricular Nucleus in Angiotensin-Induced Hypertension |
| title_full | Role of Mineralocorticoid and Angiotensin Type 1 Receptors in the Paraventricular Nucleus in Angiotensin-Induced Hypertension |
| title_fullStr | Role of Mineralocorticoid and Angiotensin Type 1 Receptors in the Paraventricular Nucleus in Angiotensin-Induced Hypertension |
| title_full_unstemmed | Role of Mineralocorticoid and Angiotensin Type 1 Receptors in the Paraventricular Nucleus in Angiotensin-Induced Hypertension |
| title_short | Role of Mineralocorticoid and Angiotensin Type 1 Receptors in the Paraventricular Nucleus in Angiotensin-Induced Hypertension |
| title_sort | role of mineralocorticoid and angiotensin type 1 receptors in the paraventricular nucleus in angiotensin induced hypertension |
| topic | hypertension sympathetic nerve activity angiotensin II aldosterone RU28318 rabbit |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.640373/full |
| work_keys_str_mv | AT sandralburke roleofmineralocorticoidandangiotensintype1receptorsintheparaventricularnucleusinangiotensininducedhypertension AT benjaminbarzel roleofmineralocorticoidandangiotensintype1receptorsintheparaventricularnucleusinangiotensininducedhypertension AT kristyljackson roleofmineralocorticoidandangiotensintype1receptorsintheparaventricularnucleusinangiotensininducedhypertension AT cindygueguen roleofmineralocorticoidandangiotensintype1receptorsintheparaventricularnucleusinangiotensininducedhypertension AT moragjyoung roleofmineralocorticoidandangiotensintype1receptorsintheparaventricularnucleusinangiotensininducedhypertension AT geoffreyahead roleofmineralocorticoidandangiotensintype1receptorsintheparaventricularnucleusinangiotensininducedhypertension AT geoffreyahead roleofmineralocorticoidandangiotensintype1receptorsintheparaventricularnucleusinangiotensininducedhypertension |