Dopamine receptor blockade and synthesis inhibition during exaggerated natriuresis in spontaneously hypertensive rats.
The influence of dopamine receptor blockade and synthesis inhibition on natriuresis induced by isotonic saline volume expansion was investigated in anaesthetized spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The aim of the study was to elucidate the mechanisms underlying the phenomenon of exaggerated natriuresis during volume expansion that has been observed in spontaneously hypertensive rats. Volume expansion, at 5% of body weight, resulted in a larger and faster natriuretic response in spontaneously hypertensive rats than in Wistar-Kyoto rats. Sixty minutes after commencement of volume expansion the natriuretic response (accumulated sodium excretion) in Wistar-Kyoto rats (n = 8) was only 24% of that in spontaneously hypertensive rats (n = 17). When spontaneously hypertensive rats were pretreated with the dopamine receptor blockers haloperidol (n = 14, 1 mg kg-1), SCH23390 (n = 8, 30 micrograms h-1 kg-1) or the dopamine synthesis inhibitor benserazide (n = 8, 50 mg kg-1; n = 5, 100 mg kg-1), the natriuretic response to volume expansion was only 16, 35, 59 and 42%, respectively, of that in untreated SHR. The corresponding proportion in the haloperidol-treated (n = 8) compared with untreated Wistar-Kyoto rats was 22%. In conclusion, isotonic volume loading results in more pronounced natriuresis in spontaneously hypertensive than in Wistar-Kyoto rats. Dopamine receptor blockade and synthesis inhibition attenuate the expansion of exaggerated natriuresis in spontaneously hypertensive rats and reduces the volume expansion natriuresis in Wistar-Kyoto rats, indicating that the dopamine system plays an important role.
Hansell
P
P
Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Sweden.
Sjöquist
M
M
D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D018492:Dopamine Antagonists; D006220:Haloperidol / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D007552:Isotonic Solutions; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000096:biosynthesis; D012965:Sodium Chloride / Q000008:administration & dosage
D018492:Dopamine Antagonists; D007552:Isotonic Solutions; D011954:Receptors, Dopamine; D012965:Sodium Chloride; D001545:Benserazide; D006220:Haloperidol