Cardiovascular effects of 6-hydroxydopamine injected into a lateral brain ventricle of the rat.

Abstract

6-Hydroxydopamine (6-OH-DA) was injected into the left lateral brain ventricle of normotensive, DOCA/NaCl or spontaneously hypertensive rats, and its effect on heart rate and blood pressure was studied. A single injection of 250 μg 6-OH-DA or 3 successive administrations of the same dose caused a reduction of noradrenaline content and tyrosine hydroxylase activity in several parts of the brain to 10–50% of the control values, indicating a considerable destruction of central adrenergic neurons. Heart rate and blood pressure decreased within 10 to 20 min after a single intraventricular injection of 6-OH-DA and both parameters returned to normal after 7 h. This effect was equally observed in normotensive and both types of hypertensive rats and regardless of whether the animals were conscious or anaesthetized. It was prevented by a prior intraventricular injection of phentolamine; this suggests that it is mediated by central alpha-adrenoceptors. The 6-OH-DA-induced bradycardia and hypotension were not influenced by a blockade of peripheral muscarinic receptors with scopolamine methylbromide; however, they were accompanied by a decrease of spontaneous discharges in the splanchnic nerve and, therefore, seem to be due to a reduction in peripheral sympathetic tone. The early cardiovascular effects of 6-OH-DA were sometimes followed by a second phase of bradycardia and hypotension. It occurred in normotensive rats 1–2 days after the second or third intraventricular injection of 6-OH-DA, and in spontaneously hypertensive rats already after a single injection. The hypotension of the second phase lasted 5–6 days, the bradycardia showed no recovery during the observation period which was limited to 3 weeks. Such long term cardiovascular effects of intraventricular 6-OH-DA were never observed in DOCA/NaCl hypertensive rats even after repeated administrations of the compound. The results provide evidence for the existence of a central adrenergic regulation of blood pressure and heart rate which seems to differ in normotensive and hypertensive rats.