scholarly journals Angiotensin II Acts in the Hypothalamic Paraventricular Nucleus to Differentially Regulate Blood pressure and Sympathetic Nerve Activity in a Rodent Model of Polycystic Kidney Disease

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Conor F. Underwood ◽  
Ahmed A. Rahman ◽  
Jacqueline K. Phillips ◽  
Cara M. Hildreth
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Paraventricular Nucleus ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Rodent Model ◽  
Polycystic Kidney ◽  
Nerve Activity

The subfornical organ drives hypertension in polycystic kidney disease via the hypothalamic paraventricular nucleus

2021 ◽  
Author(s):  
Conor F Underwood ◽  
Simon McMullan ◽  
Ann K Goodchild ◽  
Jacqueline K Phillips ◽  
Cara M Hildreth
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Paraventricular Nucleus ◽  
Subfornical Organ ◽  
Ionotropic Glutamate Receptors ◽  
Type I ◽  
Lamina Terminalis ◽  
Polycystic Kidney

AbstractAimsHypertension is a prevalent yet poorly understood feature of polycystic kidney disease. Previously, we demonstrated that increased glutamatergic neurotransmission within the hypothalamic paraventricular nucleus produces hypertension in the Lewis Polycystic Kidney (LPK) rat model of polycystic kidney disease. Here, we tested the hypothesis that augmented glutamatergic drive to the paraventricular nucleus in Lewis polycystic kidney rats originates from the forebrain lamina terminalis, a sensory structure that relays blood-borne information throughout the brain.Methods and resultsAnatomical experiments revealed that 38% of paraventricular nucleus-projecting neurons in the subfornical organ of the lamina terminalis expressed Fos/Fra, an activation marker, in LPK rats while <1% of neurons were Fos/Fra+ in Lewis control rats (P = 0.01, n = 8). In anaesthetized rats, subfornical organ neuronal inhibition using isoguvacine produced a greater reduction in systolic blood pressure in LPK vs. Lewis rats (−21±4 vs. −7±2 mmHg, P < 0.01; n = 10), which could be prevented by prior blockade of paraventricular nucleus ionotropic glutamate receptors using kynurenic acid. Blockade of ionotropic glutamate receptors in the paraventricular nucleus produced an exaggerated depressor response in LPK relative to Lewis rats (−23±4 vs. −2±3 mmHg, P < 0.001; n = 13), which was corrected by prior inhibition of the subfornical organ with muscimol but unaffected by chronic systemic angiotensin II type I receptor antagonism or lowering of plasma hyperosmolality through high-water intake (P > 0.05); treatments that both nevertheless lowered blood pressure in LPK rats (P < 0.0001).ConclusionOur data reveal multiple independent mechanisms contribute to hypertension in polycystic kidney disease, and identify high plasma osmolality, angiotensin II type I receptor activation and, importantly, a hyperactive subfornical organ to paraventricular nucleus glutamatergic pathway as potential therapeutic targets.

scholarly journals SAT-331 RENAL DENERVATION DOES NOT REDUCE BLOOD PRESSURE IN A RODENT MODEL OF POLYCYSTIC KIDNEY DISEASE

2019 ◽  
Vol 4 (7) ◽  
pp. S146
Author(s):  
S. Li ◽  
C.M. Hildreth ◽  
A.A. Rahman ◽  
V.J. Tallapragada ◽  
P.M. Pilowsky ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Denervation ◽  
Reduce Blood Pressure ◽  
Rodent Model ◽  
Polycystic Kidney

Acute inhibition of the hypothalamic paraventricular nucleus decreases renal sympathetic nerve activity and arterial blood pressure in water-deprived rats

2004 ◽  
Vol 286 (4) ◽  
pp. R719-R725 ◽  
Author(s):  
Sean D. Stocker ◽  
Kimberly J. Keith ◽  
Glenn M. Toney
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Paraventricular Nucleus ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Sympathetic Outflow ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Arterial Blood ◽  
Renal Sympathetic

The present study was performed to determine whether sympathetic outflow and arterial blood pressure in water-deprived rats are dependent on the ongoing neuronal activity of the hypothalamic paraventricular nucleus (PVN). Renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MAP), and heart rate were recorded in urethane-α-chloralose-anesthetized rats that were deprived of water but not food for 48 h before experiments. Acute inhibition of the PVN by bilateral microinjection of the GABAA agonist muscimol (100 pmol/side) significantly decreased RSNA in water-deprived rats (-26.7 ± 4.7%, n = 7) but was without effect in control rats (1.3 ± 6.3%, n = 7). Similarly, injection of muscimol produced a greater decrease in MAP in water-deprived rats than in control rats (-46 ± 3 vs. -16 ± 3 mmHg, respectively), although baseline MAP was not different between groups (105 ± 4 vs. 107 ± 4 mmHg, respectively). Neither bilateral microinjection of isotonic saline vehicle (100 nl/side) into the PVN nor muscimol (100 pmol/side) outside the PVN altered RSNA or MAP in either group. In addition, ganglionic blockade with hexamethonium (30 mg/kg iv) significantly decreased MAP in both groups; however, the decrease in MAP was significantly greater in water-deprived rats than in control rats (62 ± 2 vs. 48 ± 2 mmHg, respectively). Collectively, these findings suggest that sympathetic outflow contributes more to the maintenance of blood pressure in the water-deprived rat, and this depends, at least partly, on the ongoing activity of PVN neurons.

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