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.

No abstract

Micropuncture and histological studies were performed in dogs to characterize single-nephron adaptations to partial renal ablation. Dogs underwent sham surgery (group 1, n = 6), three-fourths nephrectomy (group 2, n = 10), or seven-eighths nephrectomy (group 3, n = 6). Single-nephron glomerular filtration rate (SNGFR) was 71.0 +/- 4.2 nl/min in group 1, 132.5 +/- 9.6 nl/min in group 2, and 161.8 +/- 12.4 nl/min in group 3 (P less than 0.05). There were parallel increases in single-nephron glomerular plasma flow rate (GPF), with a mean value of 235.3 +/- 20.1 nl/min in group 1, 442.4 +/- 34.4 nl/min in group 2, and 569.6 +/- 73.7 nl/min in group 3 (P less than 0.05, group 1 vs. groups 2 and 3). Glomerular capillary pressure, estimated from the sum of proximal tubule stop-flow pressure and arterial oncotic pressure, was 63.2 +/- 1.9 mmHg in group 1, 73.5 +/- 2.0 mmHg in group 2, and 77.9 +/- 2.2 mmHg in group 3 (P less than 0.05, group 1 vs. groups 2 and 3). The mean glomerular transcapillary hydraulic pressure gradient (delta P) in group 2 was not different from group 1 (46.8 +/- 1.3 vs. 43.9 +/- 1.8 mmHg, NS); however, it was significantly increased in group 3 (50.0 +/- 1.4 mmHg; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A B S T R A C T Experiments were done in normal rats to assess kidney, single nephron, and tubuloglomerular feedback responses during renin-angiotensin blockade with the converting enzyme inhibitor (CEI) SQ 20881 (E. R. Squibb & Sons, Princeton, N. Y.) (3 mg/kg, per h). Converting enzyme inhibition was documented by complete blockade of vascular responses to infusions of angiotensin I (600 ng/kg). Control plasma renin activity was 12.5+2.7 ng angiotensin I/ml per h (mean±SEM) and increased sevenfold with CEI (n = 7). There were parallel increases in glomerular filtration rate from 1.08±0.05 to 1.26±0.05 ml/min and renal blood flow from 6.7±0.4 to 7.5±0.5 ml/min. During CEI infusion absolute and fractional sodium excretion were increased 10-fold. Proximal tubule and peritubular capillary pressures were unchanged. Single nephron glomerular filtration rate (SNGFR) was measured from both proximal and distal tubule collections; SNGFR based only on distal collections was significantly increased by CEI. A significant difference was observed between SNGFR values measured from proximal and distal tubule sites (6.0±1.6 nl/min) and this difference remained unchanged after CEI administration. Slight decreases in fractional absorption were suggested at micropuncture sites beyond the late proximal tubule, whereas early distal tubule flow rate was augmented by CEI. Tubuloglomerular feedback activity was assessed by measuring changes in proximal tubule stop-flow pressure (SFP) or SNGFR in response to alterations in orthograde microperfusion rate from late proximal tubule sites. During control periods, SFP was decreased 11.2±0.4This work was presented in part at the Fall American Physiological Society Meetings in Miami, Florida, 1977, and at the VII International Congress of Nephrology in Montreal, Canada, 1978. Dr. Navar is the recipient of a National Heart and Lung Institute Research Career Development Award.Received for publication 7 August 1978 and in revised form 27 June 1979. mm Hg when the perfusion rate was increased to 40 nl/min; during infusion of CEI, the same increase in perfusion rate resulted in a SFP decrement of 6.7+0.5 mm Hg (P< .001). When late proximal tubule perfusion rate was increased from 0 to 30 nl/min, SNGFR was decreased by 15.0±+1.2 nl/min during control conditions, and by 11.3+1.3 nl/min during CEI infusion. Attenuation of feedback responsiveness during CEI was also observed at lower perfusion rates with both techniques. These results indicate that blockade of the renin-angiotensin system with CEI reduces the activity of the tubuloglomerular feedback mechanism which may mediate the observed renal vasodilation.

Renal autoregulation @ration rate and electrolyte excretion during vasodilatation. Am. J. Physiol. 219(3): 619-625. 1970.-The responses of the kidney to changes in renal arterial pressure were observed before and during renal vasodilatation induced by infusion of acetylcholine or papaverine directly into the renal artery. Partial abrogation of blood flow autoregulation was produced. Glomerular filtration rate, however, continued to be autoregulated at arterial pressures between 90 and 150 mm Hg.