Interlobular arteries and superficial afferent and efferent arterioles were isolated from rabbit kidney, and the effects of intraluminal pressure, norepinephrine (NE), and angiotensin II (ANG II) on lumen diameter were examined. A single microvessel was dissected and one end was cannulated. The other end of the vessel was occluded and lumen diameter was measured at fixed intraluminal pressures. With step increases in intraluminal pressure over the range of 70-180 mmHg, lumen diameters of the interlobular arteries and afferent arterioles remained constant or decreased by up to 11%. In contrast, lumen diameters of efferent arterioles continued to increase as intraluminal pressure was elevated. In all three vessels NE (10(-9) to 10(-5) M) caused a dose-dependent decrease in lumen diameter. However, only the efferent arteriole responded to ANG II (10(-12) to 10(-8) M). The contractile response of the efferent arteriole to NE or ANG II was localized to the first 50-75 micrometers of the vessel as it emerged from the glomerulus. This finding suggests that smooth muscle cells are located only in this portion of the efferent arteriole. It is concluded that at least part of the autoregulation of renal blood flow can be explained by a myogenic mechanism in preglomerular vessels and that ANG II acts primarily on postglomerular segments of the rabbit renal microcirculation.

The effects of vasopressin (AVP) and vasopressin antagonists on lumen diameters of cortical afferent and efferent arterioles isolated from rabbit kidneys were examined. Over a concentration range of 10(-14) to 10(-7) M, AVP had no effect on lumen diameters of afferent arterioles, although the arterioles were responsive to norepinephrine. Similarly, addition of 10(-8) M AVP to the lumen of afferent arterioles or to the bath of arterioles pretreated with indomethacin had no effect. In contrast, AVP caused a concentration-dependent reduction of lumen diameters of efferent arterioles. AVP was approximately 100-fold more potent than norepinephrine in producing contraction of efferent arterioles. The V1-selective antagonist, [d(CH2)5Tyr(Me)]AVP, and the V1/V2-antagonist, d(CH2)5D-Tyr(Et) desGlyVAVP, inhibited the vasoconstriction produced by AVP in a concentration-dependent but noncompetitive manner. The V2-selective antagonist, [d(CH2)5D-Ile]VAVP, had no significant effect on AVP-induced vasoconstriction. We conclude that, under the in vitro conditions used, AVP selectively contracts efferent arterioles. The results provide direct evidence for a postglomerular vascular effect of AVP in the renal cortex. This activity, together with its previously described effects on the glomerulus, suggests that AVP may produce changes in glomerular function and/or peritubular forces that are involved in tubular reabsorption.

The effects of arachidonic acid, prostaglandins (PG) I2, E2, D2, and F2 alpha on norepinephrine- (NE) and angiotensin II- (ANG II) induced tone were examined in interlobular arteries and afferent and efferent arterioles isolated from rabbit kidney. Arachidonic acid at 10(-5) M produced a rapid relaxation of NE-induced tone in all three vessel types. The vasodilatory effect of arachidonic acid but not acetylcholine was blocked by meclofenamate. In interlobular arteries, PGE2, and PGI2 caused a dose-dependent relaxation of NE-induced tone with a concentration causing the half-maximal response (ED50) of 1.2 and 4.6 X 10(-8) M, respectively. PGD2 caused a small but significant relaxation at 10(-7) M and above, whereas PGF2 alpha was inactive. In afferent arterioles contracted with NE, PGE2 and PGI2 caused identical dose-dependent relaxations. Significant effects were observed at concentrations between 10(-11) and 10(-10) M with ED50 values of 1.7 X 10(-8) M for PGE2 and 8.7 X 10(-9) M for PGI2. PGD2 had significant effects only at 10(-5) M, whereas PGF2 alpha was without effect. In contrast to the preglomerular vessels, efferent arterioles responded only to PGI2 (ED50, 9.7 X 10(-9) M), and the other arachidonic acid metabolites had no effect on lumen diameter. PGI2 antagonized the vasoconstrictive effects of both NE and ANG II in this vessel segment. The results demonstrate that of the prostanoids tested only PGE2 and PGI2 were effective in antagonizing vasoconstrictor stimuli in isolated renal microvessels. Furthermore, the rabbit renal microvasculature displays segmental heterogeneity for the vasodilatory PGs in that PGI2 affected both pre- and postglomerular arterioles, whereas PGE2 was effective only on the preglomerular microvessels.

The effect of acetylcholine (ACh), dopamine (DA), and bradykinin (BK) on vascular tone was examined in interlobular arteries and superficial afferent and efferent arterioles isolated from rabbit kidney. A single microvessel was dissected and cannulated, and lumen diameter was measured at a fixed intraluminal pressure. ACh caused a dose-dependent relaxation of norepinephrine-induced tone in all three vessel types. Significant relaxation (10-20%) was observed with 10(-8) M ACh and higher concentrations caused complete relaxation. In afferent and efferent arterioles DA caused a dose-dependent relaxation that was indistinguishable from the one caused by ACh. However, DA was much less effective on interlobular arteries. Significant relaxation was not observed until 10(-5) M DA, and 10(-4) M caused only a 30-40% relaxation. In afferent arterioles atropine blocked the effect of ACh, and metoclopramide selectively inhibited DA-induced relaxation. BK (10(-9) to 10(-5) M) caused a dose-dependent relaxation of norepinephrine-induced tone only in efferent arterioles. BK, either in the bath or lumen, had no effect on the preglomerular microvessels. ACh and DA also caused relaxation of afferent arterioles with spontaneous tone while all three vasodilators relaxed efferent arterioles with spontaneous tone. The results demonstrate segmental heterogeneity for these vasodilators in the rabbit renal microvasculature, with ACh causing relaxation in all three vessel types, DA acting primarily on the glomerular arterioles, and BK affecting only the efferent arteriole.

Although there have been a number of studies indicating a heritable component for osteoporosis in middle to late adulthood, the etiology of osteoporosis in young people is uncertain. The present study aims to evaluate the extent to which genetic factors influence familial resemblance for bone mineral density (BMD) in families ascertained on the basis of young osteoporotic probands. The sample comprises eight families (74 total individuals) that were identified through a proband under the age of 35 years with a history of two or more fractures and a spinal bone density of at least 2.5 SDs below the mean for age and sex (Z score). Secondary causes of osteoporosis were excluded in the probands.