Hydrogen sulphide acts in the subfornical organ and paraventricular nucleus to increase blood pressure (681.6)

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.

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BDNF‐Induced Changes in Synaptic Function within the Paraventricular Nucleus of the Hypothalamus (PVN) Increase Blood Pressure

The FASEB Journal ◽

10.1096/fasebj.2021.35.s1.03675 ◽

2021 ◽

Vol 35 (S1) ◽

Author(s):

Daniella Thorsdottir ◽

Zachary Einwag ◽

Benedek Erdos

Keyword(s):

Blood Pressure ◽

Paraventricular Nucleus ◽

Synaptic Function ◽

Increase Blood Pressure ◽

Induced Changes

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Corticotropin-releasing hormone projections from the paraventricular nucleus of the hypothalamus to the nucleus of the solitary tract increase blood pressure

Journal of Neurophysiology ◽

10.1152/jn.00623.2018 ◽

2019 ◽

Vol 121 (2) ◽

pp. 602-608 ◽

Cited By ~ 5

Author(s):

Lei A. Wang ◽

Dianna H. Nguyen ◽

Steve W. Mifflin

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Paraventricular Nucleus ◽

Cardiovascular Responses ◽

Solitary Tract ◽

Increase Blood Pressure ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone ◽

Optogenetic Stimulation ◽

Stimulation Of

Activation of corticotropin-releasing hormone (CRH) type 2 receptors (CRHR2) in the nucleus of the solitary tract (NTS) contributes to the development of hypertension, but the source of CRH inputs to the NTS that increases blood pressure remains unknown. This study tested the hypothesis that activation of CRH-containing projections from the paraventricular nucleus of the hypothalamus (PVN) to the NTS increase blood pressure. We expressed channelrhodopsin 2 (ChR2), a light-sensitive ion channel, into CRH-containing neurons in the PVN. This was achieved by injecting Cre-inducible virus expressing ChR2 into the PVN of CRH-Cre mice. CRH-Cre mice are genetically modified mice expressing Cre recombinase only in neurons producing CRH. We found that optogenetic stimulation of CRH-containing somas in the PVN or CRH-containing fibers in the NTS originating from the PVN significantly increased blood pressure and heart rate. Microinjection of K-41498 (CRHR2 antagonist) into the NTS attenuated the pressor and tachycardiac responses induced by optogenetic stimulation of CRH-containing somas in the PVN. In vitro loose-patch recordings revealed that optogenetic stimulation of CRH-containing fibers in the NTS originating from the PVN significantly increased the discharge frequency of NTS neurons. This effect was attenuated by pretreatment of K-41498 and was abolished by pretreatment of kynurenic acid (nonselective glutamate receptor antagonist). These results suggest that activation of PVN-NTS CRH-containing projections increases blood pressure and heart rate. The cardiovascular responses may be mediated at least in part by the corelease of CRH and glutamate from NTS CRH-containing axons originating from the PVN. NEW & NOTEWORTHY Optogenetic stimulation of paraventricular nucleus of the hypothalamus (PVN) corticotropin-releasing hormone (CRH)-containing somas or nucleus of the solitary tract (NTS) CRH-containing fibers originating from the PVN increased blood pressure and heart rate. Corelease of CRH and glutamate from NTS CRH-containing axons originating from the PVN may contribute to the pressor and tachycardiac responses elicited by optogenetic stimulation of PVN CRH-containing somas.

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Elevated brain‐derived neurotrophic factor (BDNF) levels in the paraventricular nucleus (PVN) increase blood pressure, heart rate and indices of sympathetic activity

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.1118.12 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Benedek Erdos ◽

Iara Backes ◽

Michael L McCowen ◽

Deborah A Scheuer

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Paraventricular Nucleus ◽

Neurotrophic Factor ◽

Sympathetic Activity ◽

Brain Derived Neurotrophic Factor ◽

Increase Blood Pressure

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Norepinephrine-associated left ventricular outflow tract obstruction and systolic anterior movement

BMJ Case Reports ◽

10.1136/bcr-2018-225879 ◽

2019 ◽

Vol 12 (12) ◽

pp. e225879 ◽

Cited By ~ 1

Author(s):

Warner Mbuila Mampuya ◽

Jonathan Dumont ◽

Francois Lamontagne

Keyword(s):

Blood Pressure ◽

Left Ventricular Outflow Tract ◽

Myocardial Hypertrophy ◽

Ventricular Outflow Tract ◽

Left Ventricular ◽

Outflow Tract ◽

Increase Blood Pressure ◽

Ventricular Outflow Tract Obstruction ◽

Left Ventricular Outflow ◽

Systolic Anterior Movement

In the perioperative setting, norepinephrine is used to increase blood pressure, an effect mediated mostly via arterial and venous vasoconstriction. Thus, norepinephrine is, allegedly, less likely to cause or worsen left ventricular outflow tract obstruction (LVOTO) than other inotropes. We report a case of norepinephrine-associated dynamic LVOTO and systolic anterior movement in a predisposed patient. This report highlights that unrecognised dynamic LVOTO may worsen shock parameters in patients treated with norepinephrine who have underlying myocardial hypertrophy.

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