Differential sensitivity of the pre- and postglomerular arterial vessels to vasoconstrictor activity of angiotensin II (ANG II) and norepinephrine (NE) is controversial. To avoid the complex extravascular neurohumoral variables that may have accounted for different results in the intact rat kidney, an isolated arteriole technique was used to examine the dose responses of ANG II and NE on afferent (AA) and efferent arterioles (EA) from Sprague-Dawley rats. EA were more sensitive than AA to ANG II (EC50 = 3.2 +/- 1.8 x 10(-11) and 1.0 +/- 1.6 x 10(-9) M, respectively, P less than 0.001), whereas EC50 of both AA and EA to NE were similar (3.4 +/- 2.3 x 10(-8) and 1.4 +/- 2.6 x 10(-8) M, respectively). The dose-response curves of AA to ANG II were not different when perfused at different luminal pressures (90 and 30 mmHg). In contrast, EA were more sensitive to ANG II at 30 than at 90 mmHg (3.0 +/- 1.2 x 10(-11) and 5.0 +/- 1.8 x 10(-10) M, respectively, P less than 0.005). The EC50 of EA to NE was unaffected by similar changes in luminal pressures. The mean dose-response curves of AA to ANG II were the same with and without the addition of 10(-5) M indomethacin; however, in arterioles displaying a focal constriction pattern to ANG II the response became uniform. It is concluded that, in the isolated rat glomerular arterioles, EA are more sensitive to ANG II than AA, but both vessels respond similarly to NE. The decreased ANG II sensitivity in AA is not related to the higher in vivo pressure, and the attenuated response in AA does not appear to be mediated primarily through ANG II-stimulated vasodilator prostanoid activity. EA sensitivity to ANG II appears to be inversely related to lumen pressure.

The effects of atriopeptin III (AP III) on in vitro prepared afferent (AA) and efferent arterioles (EA) from rat kidneys were tested in a system in which lumen diameter could be measured. AP III (10(-13)-10(-7) M) had no effect on lumen diameter of AA that were not preconstricted. When AA were preconstricted with either angiotensin II (ANG II) or norepinephrine (NE), however, AP III increased lumen diameter in a concentration-dependent manner to the preconstriction baseline value. Maximal vasodilation occurred at 10(-10) M AP III. Unlike AA, EA constricted by 50% to 10(-10) M AP III further constricted EA that were pretreated with ANG II or NE. Dilation in ANG II-preconstricted AA to AP III was not inhibited by indomethacin. Constriction of EA to AP III was not altered by [Sar1-Ala8] ANG II, enalapril, OKY 046, or phentolamine. Results indicate that in isolated renal arterioles AP III dilates preconstricted AA but constricts EA that have either not been pretreated or have been preconstricted with other agonists. The effect of AP III on preconstricted AA does not require vasodilator prostaglandin mediation. The constrictor effect of AP III on EA is not dependent on angiotensin, thromboxane, or alpha-adrenergic mediation.

Atrial natriuretic peptide (ANP) has been shown to reverse experimental models of ischemic acute renal failure (ARF). However, infusion of ANP has been associated with systemic hypotension making its use in clinical ARF impractical. Therefore, in this investigation, dopamine (D) was combined with intravenous (i.v.) atriopeptin III (AP III) to determine if this regimen was effective in reversing ARF while preventing systemic hypotension and maintaining renal blood flow (RBF). Four groups of Munich-Wistar rats were studied. Group 1, sham-ARF; Group 2, renal artery (RA) clamp (55 min) followed by i.v. saline; Group 3, RA clamp followed by i.v. AP III-D; and Group 4, RA clamp followed by i.v. D only. All infusions were begun after RA clamp release and continued for four hour. Mean arterial pressure in Group 3 rats given AP III-D were similar to that in Group 2, slightly less than that in Groups 1 and 4 (P less than 0.05), but consistently greater than 100 mm Hg during the four hour infusion. RBF in Group 3 was elevated above the level in Group 1 at P less than 0.05. Glomerular filtration rate (GFR), depressed by 52% in Group 2, was corrected to control (sham-ARF) levels in Group 3. In Group 4 there was a small but significant increase in GFR compared to Group 2 (P less than 0.05), but it remained less than that in sham-ARF or AP III-D treated ARF rats (P less than 0.01). Urine flow rate and urine sodium excretion rate were more than sixfold higher in Group 3 than any other group.(ABSTRACT TRUNCATED AT 250 WORDS)

The specific intrarenal sites and mechanism of endothelin (ET) vascular action are controversial. In this study afferent (AA) and efferent arterioles (EA) were isolated from the kidneys of normal Sprague-Dawley rats. Their respective concentration-dependent changes in lumen diameter in response to ET-1 were compared with those of angiotensin II (ANG II) and norepinephrine (NE). In a second series of experiments, the duration of vasoconstriction to comparable transient submaximal ET-1, ANG II, and NE concentrations in AA and EA was examined. The role of angiotensin II in mediating endothelin vasoconstriction also was examined with the converting-enzyme inhibitor captopril (CAP) and the competitive inhibitor [Sar1,Ala8]ANG II (SAR). The half-maximal constriction concentration (EC50) of ET-1 was less in EA than AA (P < 0.01). EC50 of ET-1 in AA was similar to that of ANG II, but was less than that of NE (P < 0.001). In EA the EC50 of ET-1 was also similar to that of ANG II, but much less than that of NE (P < 0.001). In both AA and EA the duration of ET-1 constriction was at least twice that of ANG II and more than fivefold that of NE. Neither CAP (10(-6) M) nor SAR (10(-7) M) changed the vasoconstrictor response to submaximal concentrations of ET-1 in AA or EA. It is concluded that ET-1 is a potent and prolonged constrictor agonist with a small, but significantly greater, concentration-dependent effect in EA than AA. The constrictor effect of ET-1 does not require ANG II activity.