Reversal of 6‐hydroxydopamine‐induced hypotension in the rat without activation of the renin‐angiotensin system.

Abstract

1. Male Wistar rats were housed individually in glass metabolic cages for 5 days during which time their food and water intakes reached plateau levels and they developed a significant systolic arterial hypertension. 2. After the initial 5-day period, systolic blood pressure and water and electrolyte balances were measured for 4 days before and 7 days after I.P. injection of 6-hydroxydopamine (100 mg/kg). In a separate experiment, plasma renin activity and glomerular filtration rate were measured 1 and 3 days after injection of 6-hydroxydopamine. Haematocrit, plasma volume, osmolality and plasma concentrations of glucose, sodium, potassium and protein were also measured at intervals after treatment. 3. Systolic blood pressure fell within 24 hr after treatment with 6-hydroxydopamine but was restored to pretreatment levels within 7 days. There was also a transient fall in glomerular filtration rate. 4. Plasma volume was significantly expanded on the first day after treatment and there was a fall in haemotocrit together with changes in plasma constituents indicative of a haemodilution, although plasma glucose levels were elevated. 5. There was a significant water retention on the third, fourth and fifth days after treatment but this was not accompanied by any measurable sodium retention and could not be attributed to renal compensation. Furthermore, plasma renin activity showed no significant change following 6-hydroxydopamine treatment. 6. It is suggested that the return of systolic blood pressure to pre-treatment levels was chiefly due to the return of vasoconstrictor function. The changes in plasma composition and volume were probably due to a fall in capillary hydrostatic pressure and an increase in the osmolality of extracellular fluid due to the elevated glucose levels.

PREVENTION AND REVERSAL OF ISOLATION-INDUCED SYSTOLIC ARTERIAL HYPERTENSION IN RATS BY TREATMENT WITH Β-Adrenoceptor ANTAGONISTS

“…It is unlikely that they acted through suppression of renin release since plasma renin levels are not elevated in isolated hypertensive animals (Gardiner & Husain, unpublished) and it is unlikely that the antihypertensive effect was centrally mediated since atenolol is reported not to cross the blood-brain barrier (Biihler, Burkart, Liutold, Kiing, Marbet & Pfisterer, 1975) whereas it was as effective as propranolol in lowering BP. The hypertension induced by short-term isolation is abolished by chemical sympathectomy with 6-hydroxydopamine (Bennett & Gardiner, 1978a), and is characterized by hyperactivity of the adrenal cortex (Bennett & Gardiner, 1978b). Elevated corticosteroid levels in isolated rats are associated with increased noradrenergic responsiveness of cardiovascular tissues, perhaps due to changes in tissue electrolyte distribution (Bennett & Gardiner, 1978b).…”

Reversal of 6-Hydroxydopamine-Induced Hypotension in Long Evans and Diabetes insipidus (Brattleboro) Rats

“…The process of the return of SBP towards normal following 6-OHDA treatment of Long Evans rats closely followed the pattern described by Bennett and Gardiner [1978] in Wistar rats, whilst the recovery of the Brat tleboro rat SBP was slower and incomplete at the end of the experiment (9 days). The SBP pattern in the first 3 days following 6-OHDA treatment was similar in both groups of ani mals.…”

“…The SBP pattern in the first 3 days following 6-OHDA treatment was similar in both groups of ani mals. The dose of 6-OHDA given to the Long Evans rats was chosen to keep the methodol ogy parallel to that of Bennett and Gardiner [ 1978]: however, this dose produced an unac ceptably high mortality rate in the Brattle boro rats; therefore, a lower dose was chosen which did not produce a fatal response, yet still seemed to give a similar hypotensive response (60 mg/kg vs. lOOmg/kg in Long Evans rats). The exaggerated hypotensive re sponse of the Brattleboro animals (which lack vasopressin) supports the view [Altura, 1980] that vasopressin may be an important ho meostatic regulator of vascular tone.…”

“…1965]. The hypoten sion induced by this treatment and the time course of the recovery from the hypotension have been described [de Champlain and van Ameringen, 1972;Yamori et al, 1972], The renin-angiotension system has been impli cated in the recovery from 6-OHDA-induced hypotension [de Champlain et al, 1975], but Bennett and Gardiner [1978] could not con firm this implication.…”

“…These were mea sured daily starting 2 days before and continuing for 9 days after 6-OHDA dosage in groups of six Long Evans rats and nine Brattleboro rats, using the tail-cuff method of Bunag [1973] as described by Bennett and Gardiner [1978], except that the rats were exposed to 32 °C environmental temperature 15 min before mea surement.…”