Downregulation of Orexin Receptor in Hypothalamic Paraventricular Nucleus Decreases Blood Pressure in Obese Zucker Rats

Redistribution of blood from the viscera to the peripheral vasculature is the major cardiovascular response designed to restore thermoregulatory homeostasis after an elevation in body core temperature. In this study, we investigated the role of the hypothalamic paraventricular nucleus (PVN) in the reflex decrease in renal blood flow that is induced by hyperthermia, as this brain region is known to play a key role in renal function and may contribute to the central pathways underlying thermoregulatory responses. In anesthetized rats, blood pressure, heart rate, renal blood flow, and tail skin temperature were recorded in response to elevating body core temperature. In the control group, saline was microinjected bilaterally into the PVN; in the second group, muscimol (1 nmol in 100 nl per side) was microinjected to inhibit neuronal activity in the PVN; and in a third group, muscimol was microinjected outside the PVN. Compared with control, microinjection of muscimol into the PVN did not significantly affect the blood pressure or heart rate responses. However, the normal reflex reduction in renal blood flow observed in response to hyperthermia in the control group (∼70% from a resting level of 11.5 ml/min) was abolished by the microinjection of muscimol into the PVN (maximum reduction of 8% from a resting of 9.1 ml/min). This effect was specific to the PVN since microinjection of muscimol outside the PVN did not prevent the normal renal blood flow response. The data suggest that the PVN plays an essential role in the reflex decrease in renal blood flow elicited by hyperthermia.

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Abstract P038: Testosterone Supplements Have Differential Effects on Blood Pressure in Old and Young Male Spontaneously Hypertensive Rats

Hypertension ◽

10.1161/hyp.66.suppl_1.p038 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Rodrigo O Maranon ◽

Licy L Yanes Cardozo ◽

Carolina Dalmasso ◽

Chetan N Patil ◽

Andrew Harris ◽

...

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Young Male ◽

Zucker Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Young Males ◽

The Metabolic Syndrome ◽

Younger Men ◽

Obese Zucker Rats

Testosterone (“T”) supplements are widely used by men to improve their quality of life, libido, and protect against osteoporosis. In clinical studies, both high and low “T” levels were found to be associated with hypertension and cardiovascular risk. Endogenous “T” levels are reduced in obese men and rats. We have shown previously that “T” supplements in middle-aged (6 mos) obese Zucker rats improved symptoms of the metabolic syndrome and caused weight loss, but increased their blood pressure. How “T” supplements affect hypertensive men and rats is unknown. We hypothesized that “T” supplements would further increase blood pressure (BP) in both old and young male spontaneously hypertensive rats (SHR). Old (O=20-22 mos) and young (Y=10 wks) male SHR were treated with “T” (testosterone propionate 8 mg/10 mm silastic pellet; OT and YT, implanted sc) or placebo (empty pellets; OP and YP, sc). Pellets were changed every 3 weeks for 8 weeks. Mean arterial pressure (MAP) was measured by telemetry for 2 weeks. MAP in OP was higher than in YP (OP: 166±7 vs YP: 148±0.5 mmHg, p<0.001). As we predicted, “T” increased MAP in YT (YP: 148±1 vs YT: 157±1 mmHg, p<0.001). In contrast, “T” decreased MAP in OT (OP: 166±1 vs OT: 155±1 mmHg, p<0.001). These data suggest that in younger men, especially men who are already hypertensive, blood pressure should be monitored closely during “T” supplementation in order to prevent further cardiovascular disease. Since “T” reduced MAP in older male SHR, these data suggest that “T” supplements may not be as detrimental in older hypertensive men as in young men. Future studies will need to be done to determine the mechanisms by which “T” increases BP in young males and the mechanisms by which “T” reduces BP in old males. Supported by NIH-R01HL66072, PO1HL51971 (JFR), 14POST18640015 (ROM), EFF Endocrine Res Grant (LLY).

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Blood pressure response to angiotensin II is enhanced in obese Zucker rats and is attributed to an aldosterone-dependent mechanism

British Journal of Pharmacology ◽

10.1111/j.1476-5381.2012.01953.x ◽

2012 ◽

Vol 166 (8) ◽

pp. 2417-2429 ◽

Cited By ~ 18

Author(s):

Helge Müller-Fielitz ◽

Margot Lau ◽

Olaf Jöhren ◽

Florian Stellmacher ◽

Markus Schwaninger ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Blood Pressure Response ◽

Pressure Response ◽

Zucker Rats ◽

Obese Zucker Rats ◽

Dependent Mechanism

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A015 Increased atrial natriuretic peptide and decreased blood pressure in fasting obese zucker rats

American Journal of Hypertension ◽

10.1016/s0895-7061(97)90823-2 ◽

1998 ◽

Vol 11 (4) ◽

pp. 34A

Author(s):

R SARZANI

Keyword(s):

Blood Pressure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Zucker Rats ◽

Obese Zucker Rats ◽

Atrial Natriuretic

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Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00439.2011 ◽

2012 ◽

Vol 302 (1) ◽

pp. H340-H348 ◽

Cited By ~ 7

Author(s):

Lusha Xiang ◽

Silu Lu ◽

William Fuller ◽

Arun Aneja ◽

George V. Russell ◽

...

Keyword(s):

Blood Pressure ◽

Tissue Injury ◽

Soft Tissue Injury ◽

Pressure Recovery ◽

Zucker Rats ◽

Orthopedic Trauma ◽

Obese Zucker Rats ◽

Blood Pressure Responses ◽

Arteriolar Tone ◽

Conscious Control

We have shown that obese Zucker rats with orthopedic trauma (OZT) exhibit a loss of arteriolar tone in skeletal muscle. We hypothesize that the loss of arteriolar tone in OZT blunts vasoconstrictor responses to hemorrhage, resulting in an impaired blood pressure recovery. Orthopedic trauma was induced with soft tissue injury and local injection of bone components in both hindlimbs in lean (LZT) and OZT (11–13 wk). One day after the orthopedic trauma, blood pressure responses following hemorrhage were measured in conscious control lean, control obese, LZT, and OZT. In another set of experiments, the spinotrapezius muscle of control and trauma animals was prepared for microcirculatory observation. Arteriolar responses to phenylephrine (PE) or hemorrhage were determined. Hemorrhage resulted in similar blood pressure responses in control animals and LZT, but the blood pressure recovery following hemorrhage was blunted in the OZT. In the spinotrapezius, OZT exhibited decreased arteriolar tone and blunted vasoconstrictor responses to PE and hemorrhage. Treatment with glibenclamide improved the blood pressure recovery in the conscious OZT and improved the arteriolar tone, and PE induced vasoconstriction in the spinotrapezius of the OZT. Thus, ATP-dependent K+ channel-mediated loss of arteriolar tone in OZT blunts the arteriolar constriction to hemorrhage, resulting in impaired blood pressure recovery.

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