No abstract

The effects of intracerebroventricularly (icv) and intravenously (iv) administered dopamine (DA) on mean arterial pressure (MAP) and heart rate were investigated in conscious spontaneously hypertensive rat (SHR), stroke-prone SHR (spSHR) and normotensive Wistar-Kyoto (WKY) rat of Japanese strains, genetically hypertensive (GHR) and normotensive (NT-NZ) rat of New Zealand strains, Sprague-Dawley (SD) rat, and left renal artery stenosed hypertensive WKY (WKYLRAS) and SD (SDLRAS) rats. Icv DA (0.0125-0.4 mg/kg) caused a linear dose-related decrease in MAP, accompanied by bradycardia in all animals. By contrast, the same doses of DA given iv caused a linear dose-related increase in MAP, accompanied by reflex bradycardia in most groups (except the spSHR, SHR and WKYLRAS where tachycardia occurred to most of the doses employed), indicating that the decrease in MAP following icv DA is centrally-mediated. A "greater" relative hypotensive effect to icv DA was seen in the Japanese hypertensive strains SHR and spSHR compared to the WKY, but not between the New Zealand strains or the renal hypertensive animals. Our data also show that this marked hypotensive responsiveness is not related to the basal MAP, but appears to be strain-specific. It is thus possible that the alleged reduced central dopaminergic activity in the Japanese strains of hypertensive rats may be responsible for exaggerated hypotensive responses observed in these strains.

The spontaneously hypertensive rat (SHR) and the stroke-prone substrain (sp-SHR) have been reported to have several abnormalities in levels of peptides both in tissue and in plasma (beta-endorphin, prolactin, thyroid stimulating hormone and vasopressin) when compared to the Wistar Kyoto (WKY) normotensive control rat. As the secretion of these peptides is under dopaminergic control and the abnormalities consistently suggest under-activity of the dopaminergic control system in the brain, injections of dopamine (0.4 mg/kg) were given i.c.v. to 10 SHR, 10 renal artery stenosis hypertensive rats (LRAS) and 10 genetically hypertensive rats of the New Zealand strain (GHR). Mean blood pressure fell from 205 +/- 6 (SEM) mmHg to 128 +/- 8 mmHg in the SHR (p less than 0.001), from 184 +/- 7 mmHg to 176 +/- 7 mmHg in the LRAS (p greater 0.05) and from 157 +/- 5 mmHg to 138 +/- 6 mmHg in he GHR (p less than 0.02). These effects were unlikely to be due to leakage of dopamine out into the periphery as i.v. dopamine (0.4 mg/kg) increased blood pressure in these animals.

In anaesthetized spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats, 0.0125-0.4 mg/kg dopamine (DA) given intracerebroventricularly (icv) produced dose-related decreases in mean arterial blood pressure (MAP) and heart rate (HR), whereas intravenous DA produced dose-related increases in MAP and HR. SHR was significantly more responsive to icv DA compared with the normotensive controls. DA (0.02 mg/kg) significantly reduced MAP in a biphasic manner, when microinjected into the arcuate nucleus or third ventricle of SHR, with no significant changes in HR. No such effect occurred in WKY rats. Metoclopramide given concurrently with DA into the third ventricle attenuated the hypotensive response to DA. Saline injection had no significant effect on MAP and HR. The hypotensive responses to DA were not confounded by the spread of injected DA into the adjacent hypothalamic areas. These results support the hypothesis that there exists an abnormal sensitivity in SHR to centrally administered DA and that the arcuate appears to be the brain site involved in this abnormality.