Increased blood pressure in mutant mice lacking D3 dopamine receptors

Document Type

Journal Article

Publication Date



Journal of Investigative Medicine






The increased renal norepinephrine (NE) release in the spontaneously hypertensive rat (SHR) may be due to an abnormal negative feedback inhibition of NE release at presynaptic dopamine Dz-like receptors. Two D2-like receptors have been cloned (D2 and D3) which may function as autoreceptors regulating NE and dopamine release from nerve terminals. These receptor subtypes are differentially expressed in kidneys of normotensive Wistar-Kyoto and SHR. D3 receptors in juxtaglomerular cells may negatively regulate renin secretion. To determine the role of the D, receptor subtype in the regulation of blood pressure (BP), homologous recombination was used to generate mutant mice lacking functional D3 receptors. Mice hetero- or homozygous to the mutant allele grew normally. However, the systolic, diastolic, and mean arterial pressures (MAP) (M±SE, mm Hg) under pentobarbital anesthesia were higher in mutant than in wild type mice (P<0.01 ANOVA, Scheffe's test). A 5% NaCl load given over 30 min did not affect BP in any of the groups Groups Wt(g) Systolic BP Diastolic BP MAP Wild Type (n=7) 34±4 101±4 79±4 89±5 Heterozyogous (n=8) 34±2 120±2 94±3 108±3 Homozygous (n=9) 31±2 120±2 96±3 109±3 Basal urine flow, Na excretion, and glomerular filtration rate were similar among the groups. The ability to excrete the 5% NaCl load was also not different among the groups. Therefore, disruption of the D, dopamine receptor results in the elevation of systolic blood pressure and development of diastolic hypertension without impairment of the ability to excrete an acute NaCl load.

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