|Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1988: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1987: ¥1,400,000 (Direct Cost: ¥1,400,000)
Renal circulation are regulated by two resistance vessels, the afferent and the efferent arterioles. Different reactions of each arteriole to endogeneous and exogenous vasoactive agents regulate renal blood flow(RBF) and glomerular filtration rate(GFR). In the present research project, the in vivo and in vitro experiments were performed to determine the sites of action of adenosine(Ad), glucagon(Gl) and acetylcholine(ACh) and the nature of an afferent arteriole isolated from the canine kidney.
1) in vivo experiments: At normal renal arterial pressure(RAP), RBF was increased by the above all agents. But, GFR was increased by Gl, decreased by Ad and unchanged by ACh. The increase in RBF by Gl occurred only at RAPs within the autoregulatory pressure range, and renal autoregulatory capability was attenuated. Contrary, Ad increased RBF at RAPs both within and below the autoregulatory pressure range, and the autoregulatory capability was not perceptibly impaired. ACh completely abolished the
autoregulation of RBF. It is generally accepted that afferent arteriolar resistance attains a minimum value at RAP near the lower limit of the autoregulatory pressure range. Thus, these data indicate that Gl and Ad preferentially dilate the afferent arteriole and the efferent arteriole, respectively, and that ACh dilates both arterioles.
2) in vitro experiments: The role of cyclic AMP(cAMP) as a second messenger of hormone or drug induced vasodilation has been proposed. A rise in intracellular cAMP concentration has been believed to be responsible for the relaxation of vascular smooth muscle by certain drugs. Then, the relationship between the dilation of isolated afferent arteriole and the cAMP accumulation induced by forskolin(Fo), a potent stimulator of adenylate cyclase. Fo(10^<-6> M) dilates the isolated afferent arteriole preconstructed with norepinephrine. Fo(10^<-5> M) produced 10-fold increase in cAMP production compared with control. Thus, the close relationship between the dilation of afferent arteriole and the cAMP accumulation. Less