The purpose of this study was to determine the specific renal microvascular segments that are functionally responsive to angiotensin II (ANG II) and other vasoactive hormones. Experiments were performed on juxtamedullary tissue from captopril-treated rats during perfusion with blood at a constant pressure of 110 mmHg. Epifluorescence videomicroscopy was utilized to measure diameters of arcuate and interlobular arteries (ART), mid- (MA) and late- (LA) afferent arterioles, and efferent arterioles (EA). Norepinephrine (700 nM) significantly decreased, and sodium nitroprusside (380 nM) increased, inside diameters of all segments. Topical application of ANG II (0.01 to 1 nM) induced significant reductions in diameters of all vessel segments: ART, 17.5 +/- 2.0%; MA, 19.6 +/- 2.5%; LA, 13.5 +/- 1.5%; and EA, 16.9 +/- 2.7%. The preglomerular response to ANG II was blocked by saralasin (10 microM) and, in most cases, was dose dependent; however, an initial hypersensitivity to low ANG II doses (30% decrease in diameter) was exhibited by 38% of the preglomerular vessels studied. Under these experimental conditions, single-nephron glomerular filtration rate decreased significantly in response to 0.01 nM ANG II exposure. These observations demonstrate that physiological concentrations of ANG II can elicit receptor-dependent and reversible vasoconstriction of the juxtamedullary nephron microvasculature at both pre- and postglomerular sites.

We conducted these experiments to evaluate the selectivity of calcium channel blockade on the renal autoregulatory mechanism and on angiotensin II-mediated renal vasoconstriction. Experiments were performed in anesthetized dogs in which renal arterial pressure, renal blood flow, and glomerular filtration rate were measured at normal and reduced renal arterial pressure. At control arterial pressures, renal arterial infusions of verapamil increased renal blood flow and glomerular filtration rate significantly. The decreases in renal vascular resistance elicited with verapamil (n = 13) and nifedipine (n = 4) occurred only at renal arterial pressure levels within the normal autoregulatory range. Renal blood flow autoregulatory efficiency was markedly attenuated, and the pressure-flow relationship obtained during calcium channel blockade approached that of a passive system. Systemic infusions of an angiotensin-converting enzyme inhibitor (captopril) during continued verapamil infusion caused further vasodilation at all renal arterial pressure values, as evidenced by an increase in slope of 27% of the pressure-blood flow relationship. This response was reversed by angiotensin II infusions. This shift indicates a reduction in minimal vascular resistance elicited by captopril, not obtainable with verapamil alone, and sensitive to angiotensin II. The effects of verapamil and nifedipine on renal blood flow autoregulation suggest a specific effect at preglomerular sites of potential operated membrane calcium channels in the autoregulatory phenomenon. The additional vasodilation elicited with captopril and reversed by angiotensin II indicates the presence of an angiotensin-sensitive postglomerular resistance component which is not influenced by calcium entry blockers.

This study was done to establish the correct relationship between protein concentration and plasma colloid osmotic pressure in the dog and to determine the possible influence of the relative albumin and globulin content (A:G ratio). Plasma samples from dogs, rats, and humans were evaluated for total protein concentration, globulin concentration, and colloid osmotic pressure. Samples were concentrated and diluted by ultrafiltration to provide a range of total protein concentrations from 1 to 12 g/dl. Rat and human plasma samples had A:G ratios of 1.4 and 2.1, respectively, and the relationship between protein concentration and colloid osmotic pressure was in agreement with the Landis-Pappenheimer equation. In contrast, dog plasma samples consistently exhibited lower colloid osmotic pressures for any given protein concentration. Two forms of empirical equations were derived to relate these parameters in the dog. Dog plasma samples had higher concentrations of globulin and the A:G ratio averaged 0.59 +/- 0.35 SD. There was a significant relationship between the A:G ratio and the plasma colloid osmotic pressure. Analysis of the possible effect of this altered relationship on glomerular filtration dynamics predicted that efferent plasma colloid osmotic pressure was not specifically affected and was dependent only on the filtration fraction and the plasma colloid osmotic pressure.

We used a model of ischemic acute renal failure featuring normal renal blood flow (RBF) to evaluate the autoregulatory capability in a preparation having a marked reduction of inulin clearance (GFR). In 10 dogs, we clamped the renal artery for 90 min (experimental); 6 dogs, 1 min only (sham). Approximately 18 hours later, we determined the autoregulatory ability from RBF responses to renal arterial constriction. GFR of the experimental dogs was 10 +/- 4 ml/min, significantly lower than GFR in the sham dogs (43 /+- 9 ml/min). RBF in the experimental dogs (189 +/- 17 ml/min) was not significantly different from that in the sham dogs (206 +/- 32). An autoregulation index, ranging from 0.49 to 1.09 (mean 0.690), was significantly larger than was that of sham dogs, which ranged from zero to 0.23 (mean 0.060). At control arterial pressures, vascular resistance was comparable in both groups; however, at reduced arterial pressures below the normal autoregulatory range, average resistance of the experimental dogs (0.62 +/- 0.12 mm Hg/[ml/min]) was significantly greater than was that of the sham dogs (0.38 +/- 0.06 mm Hg/[ml/min]). These studies indicate that a substantial loss of renal hemodynamic responsiveness follows ischemic injury to the dog even when RBF is maintained within the normal range. The loss of autoregulatory capacity associated with a severely attenuated GFR is consistent with a role for tubular flow in the normal mechanism of autoregulation.

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