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C T Hawk

Publications and source records attributed to C T Hawk.

9 recordsLinked to original sources
PubMed1996

AVP and aldosterone at physiological concentrations have synergistic effects on Na+ transport in rat CCD.

These studies examined whether the previously reported synergism between pharmacological doses of deoxycorticosterone (DOC) and arginine vasopressin (AVP) also occur at physiological concentrations of aldosterone and AVP. We examined the dose-response of salt transport, as measured by the lumen-to-bath 22Na+ flux (J1 --> b) and transepithelial voltage (VT), and of osmotic water permeability (Pf), to AVP in isolated perfused cortical collecting ducts (CCDs) from three groups of rats: (1) implanted with a 1 mg d-aldosterone pellet, which produced a moderately elevated, but physiologically relevant, plasma aldosterone concentration of 18.4 +/- 2.6 ng/dl; (2) implanted with a 2.5 mg DOC pellet (a high pharmacological dose); and (3) untreated rats, Pf reached the same maximal value in all three groups, and the concentration of AVP producing one-half the maximal Pf response (K0.5) was not significantly different among the three groups, ranging from 5 to 10 pM. There was a significantly greater increase in J1 --> b and hyperpolarization of VT with increasing AVP in both groups of treated rats than in the untreated group. The maximum values of J1 --> b and VT achieved at high AVP concentrations were not significantly different in CCDs from the aldosterone-treated and DOC-treated groups, but they were significantly higher than in the CCDs from untreated rats. Although maximal VT values achieved with DOC and aldosterone treatment were the same, the AVP K0.5 for VT were significantly lower in the DOC-treated than in the aldosterone-treated group. Although not statistically significant, the same trend was observed for J1 --> b. We conclude that AVP and aldosterone synergistically stimulate Na+ reabsorption at physiological concentrations of both hormones; however, VT (and probably Na+ reabsorption, which is generally proportional to VT) reaches maximum values at lower AVP concentrations when pharmacological doses of DOC are employed.

Aldosterone↗
PubMed1994

Sodium and water transport in cortical collecting duct of Dahl salt-resistant rat.

Studies were conducted to determine whether the cortical collecting duct (CCD) of the Dahl salt-resistant rat (inbred Rapp strain; R/Jr) exhibits the same responses to deoxycorticosterone (DOC; 2.5 mg as a depot injection in vivo, 3-8 days before experimentation) and arginine vasopressin (AVP, 220 pM in vitro) as the Sprague-Dawley (SD) [L. Chen, S.K. Williams, and J.A. Schafer. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28): F147-F156, 1990] and Dahl salt-sensitive (inbred Rapp strain, S/Jr) [C.T. Hawk and J.A. Schafer. Am. J. Physiol. 260 (Renal Fluid Electrolyte Physiol. 29): F471-F478, 1991] CCD. Qualitatively, the R/Jr CCD responded as in the other two strains: AVP elevated the osmotic water permeability (Pf, micron/s) from 0 to approximately 1,200; either AVP or DOC, when used alone, increased the lumen-to-bath 22Na+ flux (Jl-->b, pmol.min-1.mm-1) from the control range of 20-25 to approximately 40 and hyperpolarized the transepithelial voltage. AVP and DOC effects were synergistic, elevating Jl-->b to 90 +/- 5 (mean +/- SE) with both hormones, but this value was significantly lower than observed previously in both the SD and the S/Jr CCD, 125 +/- 6 and 140 +/- 6, respectively. However, bath-to-lumen fluxes (Jb--l) were also significantly lower than observed in the SD and S/Jr CCD. Because net fluxes (Jnet) in these experiments can be determined only as nonpaired differences between unidirectional fluxes, it is uncertain whether Jnet values in the R/Jr CCD are significantly lower than in the SD or S/Jr CCD.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1993

Clonidine, but not bradykinin or ANP, inhibits Na+ and water transport in Dahl SS rat CCD.

We examined the actions of potentially natriuretic autacoids in the isolated perfused cortical collecting duct (CCD) dissected from inbred Dahl (Rapp strain) salt-sensitive rats (SS). Atrial natriuretic peptide (ANP, 10 nM), bradykinin (BK, 10 nM), and clonidine (1 microM) were studied to determine their effects on the lumen-to-bath flux of 22Na+ (J1-->b, pmol min-1 mm-1), hydraulic conductivity (Pf, micron/s), and transepithelial voltage (VT, mV). ANP and BK have been shown by others to significantly reduce net Na+ reabsorption and hydraulic conductivity in the Sprague-Dawley (SD) rat CCD, but previous results from our laboratory showed no ANP or BK effect in the SD CCD. In the present study, we were also unable to observe any effect of either ANP or BK in the SS rat CCD. However, in the presence of AVP, clonidine (a partial alpha 2-adrenergic receptor agonist) significantly reduced J1-->b and Pf from 139 +/- 6 (SEM) to 88 +/- 7 and from 959 +/- 176 to 490 +/- 73, respectively. In addition, clonidine significantly depolarized VT from -14.5 +/- 2.8 to -11.2 +/- 1.8. However, unlike its effects in the SD rat CCD, yohimbine (300 nM, an alpha 2-adrenergic receptor antagonist) did not significantly reverse the effects of clonidine on J1-->b, Pf or VT in the SS rat CCD.

Animals↗
PubMed1993

Inhibition by epinephrine of AVP- and cAMP-stimulated Na+ and water transport in Dahl rat CCD.

We examined the effects of epinephrine in perfused cortical collecting ducts (CCD) isolated from inbred Dahl-Rapp salt-sensitive (SS) and salt-resistant (SR) rats and from Sprague-Dawley (SD) rats. Rats were treated with 2.5 mg deoxycorticosterone pivalate (DOC; depot injection 4-9 days before study), and the CCD were treated with 220 pM vasopressin (AVP) to maximize Na+ transport. In CCD from all three strains 10 microM epinephrine in the bathing solution completely inhibited net Na+ transport, osmotic water permeability (Pf), and transepithelial voltage. In the SS CCD, epinephrine increased the fractional resistance of the luminal membrane to the same extent as 10 microM amiloride, indicating that it blocked the amiloride-sensitive conductance of the luminal membrane. Even at 100 nM epinephrine inhibited 80-100% of Na+ and water transport, and 1 microM yohimbine reversed or prevented these effects. In SS CCD, 0.1 mM 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) plus 0.1 mM 3-isobutyl-1-methylxanthine in place of AVP increased lumen-to-bath Na+ flux (J1-->b) from 56 +/- 5 to 143 +/- 3 pmol.min-1 x mm-1 and Pf from 6 +/- 12 to 1067 +/- 152 microns/s, but 100 mM epinephrine still significantly inhibited cAMP-stimulated J1-->b and Pf by 40 +/- 5% and 31 +/- 9%, respectively. Similar results were observed in the SR and SD rat CCD; however, the ability of yohimbine to reverse the epinephrine effect on cAMP-dependent transport was variable among the rat strains. We conclude that epinephrine acts via an alpha 2-receptor to inhibit adenylate cyclase but that at least one additional intracellular second messenger system may be involved.

Adrenergic alpha-Antagonists↗
PubMed1992

Regulation of Na+ channels in the cortical collecting duct by AVP and mineralocorticoids.

A variety of experimental approaches have shown that AVP and mineralocorticoids stimulate Na+ transport through their effects on the number and kinetic properties of amiloride-sensitive Na+ channels in the apical membrane. The different mechanisms by which AVP and mineralocorticoid act on the Na+ channel provide a basis for synergism in their actions, perhaps by a scheme such as that proposed in Figure 5. However, the details of this interaction will require a better understanding of the molecular details involved in activating quiescent channels, increasing their open probability, and reorientating or inserting channels to an operational position in the apical membrane. Electrophysiological and biochemical approaches have gone a long way toward elucidating some of these molecular details. But the latter approach in particular has indicated that the Na+ channel may have multiple regulatory subunits and thus be a target for several intracellular second messengers and autacoids other than those involved in the actions of AVP and aldosterone. The challenges for future research in this area are multiple. It seems likely that the primary amino acid sequence of the channel subunits will soon become available from cloning and sequencing approaches, but the application of this knowledge to understanding how the subunits are integrated into the complete protein and mediate regulatory signals will be a formidable task. It will be important to determine the normal extracellular signals (other than aldosterone and AVP) and the associated intracellular second messengers that alter channel activity. It will also be important to understand how some species such as the rabbit may "turn off" the stimulatory effect of AVP on Na+ reabsorption in the CCD, and how this regulatory process is altered when these cells are cultured. At the whole animal level, it will also be important to investigate whether changes in one or more of the normal regulatory pathways that impinge on the Na+ channel might be involved in a diminished ability to excrete a salt load, as is observed in some models of hypertension. All of these issues need to be understood at the molecular level, and it seems likely they will provide exciting physiological insights at all levels.

Aldosterone↗
PubMed1991

Effects of AVP and deoxycorticosterone on Na+ and water transport in the Dahl salt-sensitive rat CCD.

Cortical collecting ducts (CCD) from inbred Dahl salt-sensitive rats were perfused in vitro to study effects of arginine vasopressin (AVP, present in the bath) and deoxycorticosterone pivalate (DOC) pretreatment on lumen-to-bath and bath-to-lumen fluxes of 22Na+ (J1----b and Jb----1 in pmol.min-1.mm-1, respectively), hydraulic conductivity (Pf, microns/s), and transepithelial voltage (VT, mV). J1----b was 37.1 +/- 5.3 (mean +/- SE) in untreated rats and increased to 83.2 +/- 15.9 with AVP. VT increased from -0.3 +/- 0.6 to -7.0 +/- 2.0. In DOC-pretreated rat CCDs, baseline J1----b was higher (85.1 +/- 7.6) as was VT (-11.3 +/- 1.7); J1b----b and VT were doubled with AVP addition (185.6 +/- 18.6 and -21.7 +/- 2.3, respectively). Thus J1----b in AVP-stimulated CCDs from untreated rats was not significantly different from control (no AVP) J1----b from DOC-pretreated rats; however, AVP produced a greater J1----b increase in the latter CCDs. Neither AVP nor DOC had an effect on Jb----1, which ranged from 25 to 50. Benzamil reduced J1----b to values not significantly different from Jb----1, and VT became zero in CCDs treated with both AVP and DOC, indicating Na+ transport stimulated by both hormones occurs through apical membrane Na+ channels. Pf increased from 59 +/- 80 to 1,072 +/- 176 with AVP addition to untreated rat CCDs and was unaltered by DOC or benzamil. Thus the Dahl rat CCD exhibits a transport response to AVP and DOC that is indistinguishable from that observed in Sprague-Dawley rats, as previously reported by this laboratory.

Absorption↗
PubMed1984

Tetraethylammonium transport by isolated perfused snake renal tubules.

Tetraethylammonium (TEA) transport was studied in isolated perfused snake (Thamnophis spp.) proximal renal tubules. Unidirectional lumen-to-bath (J1----bTEA) and bath-to-lumen (J1----bTEA) fluxes exhibited saturation kinetics, but Jb----1TEA also exhibited an apparent diffusive component and J1----bTEA did not. Jb----1TEA exceeded J1----bTEA at all concentrations studied, resulting in net TEA secretion. Transport into cells across both luminal and peritubular membranes was apparently against an electro-chemical gradient and was inhibited by cyanide. Km for J1----bTEA (5.9 microM) was about one-third Km for Jb----1TEA (19.9 microM), indicating greater affinity of the luminal transporter for TEA; but Vmax for Jb----1TEA (153 fmol X min-1 X mm-1) was about six times Vmax for J1----bTEA (27 fmol X min-1 X mm-1), indicating a greater capacity of the peritubular transporter for TEA, which could account for net TEA secretion. Jb----1TEA was inhibited by N-methylnicotinamide (NMN) in the bath, but J1----bTEA was inhibited initially and then apparently transstimulated by NMN in the lumen, indicating possible countertransport. J1----bTEA, but not Jb----1TEA, was significantly reduced by replacement of sodium with sucrose, indicating possible sodium dependency of the luminal transporter. All data indicate active (either primary or secondary) TEA transport at both luminal and peritubular membranes but net transepithelial transport in the bath-to-lumen direction.

Animals↗
PubMed1980

Renal excretion of urea in the salamander, Ambystoma tigrinum.

Renal excretion of urea was assessed in adult and larval Ambystoma tigrinum by comparing simultaneous clearances of urea and inulin. The mean adult urea clearance ratio (CU/CIn) was 0.70 +/- 0.08 indicating net urea absorption. Larvae yielded a mean CU/CIn of 0.92 +/- 0.04. Individual larvae were quite variable however as approximately 30% displayed CU/CIn > 1. There was a significant negative correlation between CU/CIn and fractional water reabsorption. Comparisons of larval kidney urea concentration (KU) and plasma urea concentration (PU) revealed a mean KU/PU of 1.43 +/- 0.15. Treatment with 2,4-dinitrophenol decreased larval CU/CIn to 0.80 +/- 0.05 and KU/PU to 0.91 +/- 0.08. Phloridzin also decreased CU/CIn (0.67 +/- 0.06) however para-aminohippuric acid had no effect. Hypophysectomy combined with cautery of the pituitary stalk resulted in CU/CIn of 1.71 +/- 0.33 as compared to 0.84 +/- 0.08 in shams. These results are consistent with the possibility of net urea secretion at some point in the A. tigrinum nephron, followed by passive reabsorption in the distal segments under the influence of antidiuretic hormone.

Animals↗