Involvement of endogenous central hydrogen sulfide (H₂S) in hypoxia-induced hypothermia in spontaneously hypertensive rats

Abstract

Spontaneously hypertensive rats (SHR) display autonomic imbalance and abnormal body temperature (Tb) adjustments. Hydrogen sulfide (HS) modulates hypoxia-induced hypothermia, but its role in SHR thermoregulation is unknown. We tested the hypothesis that SHR display peculiar thermoregulatory response to hypoxia and that endogenous HS overproduced in the caudal nucleus of the solitary tract (NTS) of SHR modulates this response. SHR and Wistar rats were microinjected into the fourth ventricle with aminooxyacetate (AOA, HS-synthezing enzyme inhibitor) or sodium sulfide (NaS, HS donor) and exposed to normoxia (21% inspired O) or hypoxia (10% inspired O, 30 min). Tb was continuously measured, and HS production rate was assessed in caudal NTS homogenates. In both groups, AOA, NaS, or saline (i.e., control; 1 μL) did not affect euthermia. Hypoxia caused similar decreases in Tb in both groups. AOA presented a longer latency to potentiate hypoxic hypothermia in SHR. Caudal NTS HS production rate was higher in SHR. We suggest that increased bioavailability of HS in the caudal NTS of SHR enables the adequate modulation of excitability of peripheral chemoreceptor-activated NTS neurons that ultimately induce suppression of brown adipose tissue thermogenesis, thus accounting for the normal hypoxic hypothermia.

A Case for Hydrogen Sulfide Metabolism as an Oxygen Sensing Mechanism

“…Sabino et al, [ 162 ] reported that microinjection of aminooxyacetate (AOA) into the fourth ventricle of Wis-tar normotensive rats (WNR) did not affect the cardiovascular responses to hypoxia (30 min of 10% inspired O 2 ), whereas it blunted the ventilatory and cardiovascular responses in SHR rats. The same group also demonstrated that H 2 S modulates hypoxia-induced hypothermia in rats, and this is also exacerbated in spontaneously hypertensive (SHR) rats due to excess H 2 S production in the caudal nucleus of the solitary tract [ 163 ]. These findings support a link between H 2 S and O 2 .…”

CBS‐Induced H2S Generation in Hippocampus Inhibits EA‐Induced Analgesia

“…Coordinates of A-P: 2.5 mm relative to the bregma, lateral: ±2.5 mm relative to the midline, and depth: 2 mm from the duramater were used for implanting guide cannulas (RWD, China) into the bilateral hippocampi [22]. After recovery from surgery, HA (9 nmol/1 μl [23]), AOAA (9 nmol/1 μl [24,25]), or SAM (10 pmol/1 μl [26]) was bilaterally microinjected into the hippocampi. DAO and CAT inhibitors followed the same procedure.…”

“…ermal Hypersensitivity. To study the relationship between CBS-induced H 2 S in the brain and thermal hypersensitivity, the CBS inhibitor HA (9 nmol) [23] or AOAA (9 nmol) [24,25] was bilaterally microinjected into the hippocampus. Moreover, the CBS-specific agonist SAM (10 pmol) [26] or saline was also bilaterally injected into the hippocampus one day after CFA injection, and CAT and DAO inhibitors [37] followed the same procedure (Figure 3(a)).…”

Circadian Rhythms of Body Temperature and Locomotor Activity in Spontaneously Hypertensive Rats under Frequent Changes in Light Conditions

“…Rats with spontaneous hypertension (SHR—Spontaneously Hypertensive Rat) demonstrate autonomic imbalance and abnormal body temperature regulation [ 29 ]. It should be noted that the increase in blood pressure in animals of the SHR line begins at the age of 6 weeks, reaching systolic pressure between 180 and 200 mm Hg in adulthood [ 30 ].…”