The effects of angiotensin II (ANG II) or angiotensin III (ANG III) on renal cortical blood flow (CBF) or papillary blood flow (PBF) were investigated in Inactin-anesthetized young rats with the use of laser-Doppler flowmetry. Infusion of equimolar pressor doses of ANG II (300 ng.kg-1.min-1 iv) or ANG III (267 ng.kg-1.min-1) decreased CBF by 31 +/- 2.6% (P less than 0.001) and 20.3 +/- 3.2% (P less than 0.01), respectively but increased PBF by 19 +/- 6.1% (P less than 0.05) and 14.6 +/- 4.4% (P less than 0.05). The ANG II-induced increase in PBF was not prevented by aortic clamping to maintain constant renal perfusion pressure or pretreatment with the prostaglandin synthase inhibitor, indomethacin. The nonpeptide ANG II receptor antagonist, DuP 753 completely abolished the systemic and intrarenal effects of ANG II. After pretreatment with a kallikrein inhibitor, aprotinin, ANG II infusion increased mean arterial pressure but did not affect PBF, suggesting that kinins, but not prostaglandins, modulate the action of systemic ANG II on PBF. We conclude that circulating ANG II induces vasoconstriction in the cortex and also promotes the intrarenal production of kinins, which act to enhance papillary blood flow.

In autoradiographic studies in anesthetized rats, 125I-labeled amylin binding was associated with proximal convoluted tubules but not distal tubules, interstitium, or glomeruli in the renal cortex. Split-drop micropuncture experiments showed that perfusion of the peritubular capillaries with amylin (10(-9) M) stimulated proximal tubular fluid absorption by 28%. This effect was inhibited by luminal addition of ethylisopropylamiloride, indicating mediation by a brush-border Na+/H+ exchanger. Intravenous infusion of an amylin binding antagonist, AC-187, reduced proximal fluid reabsorption (22%) in anesthetized rats, indicating a role for endogenous amylin in salt homeostasis. In primary cultures of rat proximal tubule cells, amylin (10(-7) M) stimulated proliferation with a potency equal to epidermal growth factor. Peptide antagonists (AC-187, AC-413, and AC-512) of the amylin binding sites in the renal cortex blocked the mitogenic action of amylin. We conclude that amylin acts on renal proximal tubules to promote sodium and water reabsorption and cell proliferation. These novel actions may have implications for the development of hypertension for example in non-insulin-dependent diabetes mellitus and obesity in which hyperamylinemia has been observed.

Total Kupffer cell phagocytic activity of the liver is markedly increased in rats with a high parasitemic load of malarial P. berghei infection. This is presumed to reflect an upregulation of scavenger activity phagocytosing erythrocytes and their breakdown products.

We have previously reported that amylin has mitogenic actions on tubular epithelial cells isolated from mature rat kidney and cultured in vitro. In experiments using in situ hybridization, we have demonstrated that amylin mRNA can be detected transiently in rat metanephros from embryo day 17 (E17) to postnatal day 3 (PN3). These transcripts are localized in the sub-nephrogenic zone. RT-PCR was performed using oligonucleotide primers for rat amylin and mRNA extracted from fetal body (E19), PN1 and PN5 metanephroi, and adult rat kidney. These results corroborate the finding, using in situ hybridization, that there is a window of expression of rat amylin in the developing kidney in the perinatal period. During this period tubular elongation is evident and amylin peptide, detected by immunohistochemical staining, is found associated with developing tubules. Some of these tubules also express a brush border glycoprotein, detected by immunohistochemical staining. Amylin acts as a mitogen with primary cultures of proximal tubular epithelial cells from PN4 renal cortex. An amylin antagonist inhibited this mitogenic action suggesting that this was mediated by amylin receptors as previously described. We suggest that amylin peptide is biosynthesized in the developing proximal tubules, acts in an autocrine fashion to promote the proliferation and differentiation of brush border epithelial cells and hence plays an important role as a growth factor in the development of the kidney.