Reemergence of spontaneous hypertension in hypoxia-protected rats returned to normoxia as adults.

Five-week-old male spontaneously hypertensive rats (SHR) were either exposed to hypoxia or maintained in normoxia. Groups of rats were returned to normoxia after 8 or 12 weeks exposure to hypoxia while others remained in hypoxia or normoxia throughout the study. Subdivisions of the groups were sacrificed 2 or 6 weeks after return to normoxia at the same time as were rats continuously exposed to either normoxia or hypoxia. Hypoxia attenuated the development of systemic hypertension (P less than 0.05); however, this protection dissipated partially when rats were returned to normoxia. Norepinephrine concentration was significantly elevated and serotonin turnover (5-hydroxyindoleacetic acid/serotonin 5HIAA/5HT) was significantly decreased in caudal brainstem of hypoxic SHR and both were gradually normalized upon return to normoxia. Similarly, left ventricular hypertrophy was attenuated and adrenal catecholamine contents were increased with hypoxic exposure. Both gradually normalized upon return to normoxia. Mechanisms associated with the development of spontaneous hypertension reemerge when adult, previously hypoxic SHR are returned to a normoxic environment. These findings implicate long-term changes in central noradrenergic and serotonergic function as components of the cardiovascular adaptation to hypoxia which includes hypoxic moderation of spontaneous hypertension.

Hypoxic attenuation of brain stem serotonin does not influence sodium-induced hypertension.

Sodium (Na+)-dependent hypertension was studied in hypoxia in an effort to determine the basis for hypoxia-mediated attenuation of hypertension. Hypoxia attenuated spontaneous hypertension while Na+ increased blood pressure in SHR. A lack of interaction between the effects of hypoxia and Na+ indicated additivity of effects. As a result, hypoxia-exposed, Na(+)-supplemented SHR had similar blood pressure as did normoxic, nonsupplemented SHR although both groups had lower blood pressure than normoxic, Na(+)-supplemented SHR. Hypoxia decreased serotonin turnover (5-HIAA/5-HT) in the brain stem of SHR while supplemental Na+ had no influence on this measurement. Hypoxic exposure in DOCA-treated rats failed to prevent the development of hypertension although hypoxia decreased 5-HIAA/5-HT in the brain stem of hypoxic rats, irrespective of DOCA treatment. The finding in SHR that Na+ counteracts the protection of hypoxia could be argued to support a similar mechanism of action for hypoxia and sodium. However, the results with DOCA treatment clearly refute such an interpretation. Our findings indicate that the pressor influence of Na+ does not occur through the modulation of brain stem 5-HIAA/5-HT.

Hypothyroidism increases serotonin turnover and sympathetic activity in the adult rat.

Adult, male Sprague-Dawley rats underwent surgical thyroidectomy (Tx) or sham surgery. In all three experiments from which data are reported, a 3-week recovery period was allowed. In experiments I and II, baseline measurements of colonic temperature (Tc) and urinary norepinephrine excretion (NE) were obtained, and both variables were monitored daily for the duration of the studies. After baseline measurements, half of each surgical group was given either triiodothyronine (T3) or vehicle injections subcutaneously; in experiment I replacements continued for 1.5 days, while in experiment II T3 replacement continued for 3.5 days. Rats were decapitated at the end of each experiment and serotonin (5-HT) turnover was measured in brainstem. Serotonin turnover in rostral and caudal brainstem was increased with Tx (p less than 0.05). Increased turnover in caudal brainstem was normalized by T3 only in experiment II. Similarly, decreased Tc and elevated NE with Tx were normalized in experiment II but not in experiment I. In experiment III, NE measurements normalized on a creatinine excretion basis indicated that increased NE is evident with Tx, irrespective of normalization procedure. Significant correlations between 5-HT in caudal brainstem and metabolic correlates of sympathetic function, concurrent normalization of NE and 5-HT in caudal brainstem, plus work from other laboratories describing sympathoexcitatory serotonergic neurons located in the caudal brainstem suggest that the central and peripheral changes in the hypothyroid rat are causally related.