Biomedical subjects

C Horton

Publications and source records attributed to C Horton.

At least 73 records · Page 4Linked to original sources

PubMed1995

Three weeks of ganciclovir for cytomegaloviraemia after allogeneic bone marrow transplantation.

Cytomegaloviraemia diagnosed by early antigen detection or conventional viral culture from blood occurred 7-71 days (median 41 days) after transplant in 25 of 38 consecutive patients undergoing bone marrow transplantation (BMT) from HLA-identical siblings for haematological malignancies where patient and/or donor were CMV-seropositive. Prophylactic ganciclovir, high-dose intravenous acyclovir or immunoglobulin were not administered. Viraemia was treated with a short 3-week course of ganciclovir (10 mg/kg x 1 week, 5 mg/kg x 2 weeks). Clearance of viraemia occurred 3-47 days (median 6 days) after starting anti-viral therapy in 20 patients (18 with ganciclovir, 2 with foscarnet), and before therapy in 3 patients. The remaining 2 patients received inadequate anti-viral therapy for various reasons and died of CMV pneumonitis. There was no clinical evidence of CMV disease in the 13 patients who did not develop viraemia. One patient treated with ganciclovir before adequate haematological recovery died of graft failure. A second episode of viraemia occurred in four patients, and a third in one. We conclude that a short 3-week course of ganciclovir is adequate in most patients developing cytomegaloviraemia after allogeneic BMT. Treatment is not necessary in all patients but some inadequately treated patients develop CMV disease. Ganciclovir is tolerated well but may cause severe myelosuppression if used prior to adequate marrow recovery.

Adolescent↗

PubMed1995

Maintenance therapy for remission in myeloma with Intron A following high-dose melphalan and either an autologous bone marrow transplantation or peripheral stem cell rescue.

Eighty-four patients with myeloma were randomized to receive maintenance Intron A (Schering-Plough, Suffolk, UK), 3 mega units/m2 s.c. three times weekly or no treatment following induction therapy with cyclophosphomide, vincristine, doxorubicin, methyl prednisolone (C-VAMP), consolidated with high-dose melphalan (HDM) 200 mg/m2 + autologous bone marrow transplantation (ABMT). The patients have been followed up for a median of 52 months. Overall, median progression-free survival (PFS) from HDM was 27 months in the control group and 46 months in the Intron A group (< 0.025). For the 65 patients who achieved complete remission (CR) with HDM, there was a significant prolongation of remission (p = 0.02) for those who received Intron A and 49% of these patients remained in remission four years after high-dose treatment. However, for partial responders (PR) and nonresponders to HDM there was no significant prolongation of PFS. Overall, survival was also significantly better for the Intron A group, with 5 deaths versus 14 deaths in the control group (p = 0.006). Subsequently, 54 consecutive patients received the same HDM followed by rescue with peripheral blood stem cells after induction chemotherapy which included C-VAMP. Intron A was started in 45 of these patients at a median of 62 days which was comparable to the ABMT arm. The overall response rate in these patients was 79.62% (43/54-CR+PR) and the probability of survival at 18 months was 74.2% by the Kaplan Meier method.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Autologous bone marrow transplantation for acute myeloid leukemia in first remission: identification of modifiable prognostic factors.

Seventy-four consecutive patients (median age 31 years) with acute myeloid leukemia (AML) undergoing unpurged autologous bone marrow transplantation (ABMT) in first remission after melphalan and total-body irradiation were studied to assess the impact of 14 modifiable and non-modifiable prognostic factors on relapse and disease-free survival. Thirty patients were alive in continuous CR at a median of 37.5 months (range 3-94), 14 died of transplant-related toxicity at a median of 5.5 months (range 0.5-18), and 30 relapsed at a median of 7.5 months (range 2-23). The actuarial 5-year probabilities of relapse and disease-free survival were 53.4 and 34.2%, respectively. On multivariate analysis, administration of two or more courses of consolidation chemotherapy prior to the harvest and transplant was found to be the most significant factor associated with decreased relapse (relative risk 2.62, P = 0.0012) and improved disease-free survival (relative risk 3.03, P = 0.0009). A nucleated cell dose of > 2 x 10(8)/kg improved disease-free survival (relative risk 2.17, P = 0.045) by decreasing transplant-related mortality (P = 0.047). We conclude that adequate consolidation of remission before ABMT is the most important factor associated with continuing remission after ABMT. Short-term therapy of AML with two courses of consolidation therapy followed by ABMT requires comparison with repeated courses of intensive chemotherapy for efficacy and cost-effectiveness.

Adolescent↗

PubMed1994

Increasing the efficiency of emergency medical services by using criteria based dispatch.

STUDY OBJECTIVES: To determine whether criteria based dispatch (CBD) improved the efficiency of the emergency medical services system. DESIGN: A before and after design was used to measure effects of CBD. Data were reviewed from medical reports from January 1986 through June 1992. SETTING: King County, Washington, excluding the city of Seattle. PARTICIPANTS: Residents who called 911 to report a medical emergency. INTERVENTIONS: Emergency medical dispatching (EMD), basic life support (BLS), and advanced life support (ALS). RESULTS: Findings show a decrease in ALS responses for two tracer conditions that medical control physicians determined not require ALS intervention. The percentage of febrile seizures in which paramedics responded decreased from 41% to 21% (P < .001). The percentage of cerebrovascular accidents in which paramedics responded decreased from 41% to 28% (P < .001). CBD led to a decrease, from 4.7% to 3.8% (P < .001), in frequency of requests by BLS units for dispatch of ALS units. There was no increase in the time required to dispatch each call. CONCLUSION: CBD increased the efficiency of the EMS system by significantly reducing ALS responses to incidents not requiring ALS intervention and reducing requests by BLS units for dispatch of ALS units while maintaining a consistent time from receipt of call to dispatch.

Cerebrovascular Disorders↗

PubMed1994

Immunolocalization of matrix metalloproteinases and TIMP-1 (tissue inhibitor of metalloproteinases) in human gingival tissues from periodontitis patients.

The matrix metalloproteinases (MMPs) collagenase, gelatinase A (72 kDa gelatinase), stromelysin, and their specific inhibitor TIMP-1 (tissue inhibitor of metalloproteinases), were immunolocalized using specific polyclonal antisera in gingival tissues from 21 patients with chronic inflammatory periodontal disease. Monoclonal antibodies against macrophages (Leu-M5), B cells (Leu-14), helper T cells (OKT4), suppressor T cells (OKT8) and the HLA-DR epitope were also used to identify leukocyte subsets. MMPs were observed in connective tissues at sites that histologically showed signs of remodelling. The number and distribution of positive cells varied widely, however, not only between individual biopsy specimens, but also within the same specimen. The same was true for the composition and distribution of the inflammatory cell infiltrate. Moreover, although there was a positive correlation between the number of MMP-producing cells and the severity of inflammation in some specimens, for others with comparable leukocyte subset scoring the number was reduced and sometimes absent altogether. Cells secreting MMPs were fibroblasts, macrophages and epithelial cells. It was not possible to determine unequivocally whether a MMP-positive cell within the connective tissue was a fibroblast or a macrophage, since the antisera recognise both fibroblast and macrophage MMPs and the different fixation requirements for MMPs (4% paraformaldehyde) and Leu-M5 (acetone) precluded co-localization on the same section. TIMP-1 was immunolocalized within connective tissue cells at sites of tissue remodelling. Our results support the hypothesis that tissue-derived MMPs may be involved in tissue remodelling in periodontal disease and conclusively demonstrate that epithelial cells may be involved as well as connective tissue cells.

Antibodies, Monoclonal↗

PubMed1994

Bone marrow transplantation for primary refractory acute leukaemia.

Twenty-four patients with primary resistant acute leukaemia received bone marrow transplants (BMTs) from matched sibling, syngeneic, matched unrelated, or mismatched family donors as treatment for induction failure. Three (12.5%) patients are alive and well 2-10 years after transplantation. Four (16.7%) patients died of transplant-related complications early post-transplant and remission status could not be determined. Two patients did not achieve complete remission (CR) and died of cytomegalovirus pneumonitis 3 months post-transplant. One patient died of graft failure. CR was obtained in 17 of 20 (85%) evaluable patients after BMT. Ten of 17 (58.8%) patients achieving CR died of transplant-related complications 1-10 months post-transplant. Four of 17 (23.5%) patients who had achieved CR relapsed after transplant. We conclude that a high proportion of patients failing to achieve remission with aggressive conventional chemotherapy achieve CR with BMT and a small proportion become long-term survivors.

Adolescent↗

PubMed1992

Domains of cellular retinoic acid-binding protein I (CRABP I) expression in the hindbrain and neural crest of the mouse embryo.

We describe here the distribution of cellular retinoic acid-binding protein I (CRABP I) in the head of the early mouse embryo from day 8 to day 13 of gestation, using both in situ hybridisation to localise mRNA and immunocytochemistry to localise protein. The distribution of mRNA and protein was found to be identical. CRABP I first appeared in part of the presumptive hindbrain of the presomite embryo and then became localised to rhombomeres 2, 4, 5 and 6. The only other area of expression in the cephalic neuroepithelium was in a part of the midbrain roof. The neural crest and its mesenchymal derivatives, the branchial arches, expressed CRABP I and crest could be seen streaming from the neuroepithelium of individual rhombomeres into particular branchial arches. This suggested a fate map could be constructed describing the rhombomeric origin of branchial arch mesenchyme. Later in development, axons throughout the hindbrain expressed CRABP I. The results are considered in terms of the role of retinoic acid in the specification of neuronal phenotype in the hindbrain and in axon outgrowth.

Amino Acid Sequence↗

PubMed1991

Inhibition of mineralization of glutaraldehyde-pretreated bovine pericardium by AlCl3. Mechanisms and comparisons with FeCl3, LaCl3, and Ga(NO3)3 in rat subdermal model studies.

In the present study, the authors investigated the mechanism by which Al3+ preincubations inhibited the pathologic calcification of glutaraldehyde-pretreated bovine pericardium (GPBP) implanted subdermally in rats. The concentration dependency of the Al3+ anticalcification effect was compared with that of other trivalent metal ions (Fe3+, Ga3+, La3+) known to interact with calcium phosphates. In vitro incubations of GPBP were carried out in AlCl3 (10(-3) mol/l [molar] to 10(-1) mol/l) to ascertain both the optimal conditions for uptake of Al3+ and the time course of Al3+ dissociation. Al3+ uptake by GPBP was concentration dependent and occurred rapidly, with tissue levels after 1 hour not differing significantly from those after 72 hours of incubation. Analyses of GPBP samples preincubated in AlCl3 (0.1 mol/l, 24 hours) showed that more than 75% of the Al3+ remained tightly bound after 60 days' in vitro release at 37 degrees C, pH 7.4. Preincubations of GPBP in AlCl3 significantly inhibited calcification after subdermal implantation in rats for 60 days (Ca++ = 5.1 +/- 0.9 microgram/mg, 11.5 +/- 4.6 micrograms/mg, 70.3 +/- 23.0 micrograms/mg, mean +/- standard error [SE], for 10(-1) mol/l, 10(-2) mol/l, 10(-3) mol/l AlCl3, respectively), compared with controls (Ca++ = 110.0 +/- 9.3 micrograms/mg). All animals were free of Al3(+)-mediated adverse effects on bone, as determined by light microscopic evaluation of femoral epiphyseal growth plates. Transmission electron microscopy coupled with electron energy loss spectroscopy (EELS) of GPBP incubated in 10(-1) mol l AlCl3 for 24 hours demonstrated discrete Al3+ localization in the sarcolemma and cytoplasmic and nuclear membranes of devitalized pericardial connective tissue cells at intracellular sites coincident with phosphorus loci. Similar intracellular localization remained prominent in explants removed after 60 days; no calcific deposits were noted in these specimens. Preincubations in Fe3+ but not Ga3+ and La3+ solutions yielded significant inhibition of GPBP calcification, which did not differ significantly from that provided by Al3- and had a comparable concentration dependency. Light microscopic examination (Prussian blue staining) and EELS of FeCl3-preincubated explants demonstrated Fe3+ localization within devitalized GPBP connective tissue cells. The authors conclude that Al3+ and Fe3+ significantly inhibit the pathologic mineralization of glutaraldehyde-pretreated bovine pericardium by mechanisms that are likely related to the high affinity of these cations for membrane associated and other intracellular phosphorus loci.

Aluminum↗

PubMed1990

Direct visualization of effects of endothelin on the renal microvasculature.

The renal microvascular and hemodynamic actions of endothelin were assessed directly in isolated perfused hydronephrotic (HYD) and normal kidneys, respectively. In HYD kidneys endothelin was a potent vasoconstrictor of the afferent arteriole (AA), eliciting a threshold vasoconstrictor response at 0.01 nM (P less than 0.05). At 0.1 and 0.3 nM, endothelin reduced AA diameter by 22 +/- 6 (P less than 0.025) and 41 +/- 4% (P less than 0.001), respectively. Furthermore, endothelin provoked oscillatory vasomotion in the AA. In contrast, endothelin had less effect on the efferent arteriole (EA), reducing EA diameter by only 7 +/- 4 (P greater than 0.20) and 13 +/- 4% (P less than 0.05), at 0.1 and 0.3 nM, respectively. In normal kidneys endothelin elicited a long-lasting vasoconstriction with a dose dependency similar to that observed in the AA of HYD kidneys. Furthermore, endothelin reduced glomerular filtration rate (GFR) from 0.58 +/- 0.04 to 0.09 +/- 0.05 ml.min-1.g-1 (P less than 0.001) in this model. Both the AA vasoconstriction and reduction in GFR were completely reversed by nifedipine. These findings indicate that endothelin is a potent renal vasoconstrictor that decreases GFR by a predominant vasoconstriction of the AA. Our observations are consistent with the postulate that endothelin elicits renal vasoconstriction via a mechanism involving dihydropyridine-sensitive calcium channels and that such calcium channels play a prominent role in the activation of the AA.

Animals↗

PubMed1990

Examination of relative rates of cAMP synthesis and degradation in crude membranes of adipocytes treated with hormones.

The impact of changes in the activation state of the low Km cAMP phosphodiesterase (PDE) on cAMP output in adipocyte membranes was assessed by measuring the product of cAMP synthesis and degradation in the membrane preparation simultaneously. Crude membranes were prepared from adipocytes treated with the cAMP analog, 8-pCl phi S-cAMP and from adipocytes treated with 2 nM insulin. Using membranes from control and treated cells, adenylate cyclase was activated with various concentrations of forskolin and cAMP production (synthesis minus degradation) was measured with and without complete PDE inhibition using the specific inhibitor CI-914. Half maximal inhibition of the low Km cAMP PDEs in control membranes was produced by 1.16 +/- 0.07 microM CI-914 and greater than 98% of the activity was inhibited by 100 microM CI-914. The I50 and the concentration of CI-914 producing complete PDE inhibition in membranes from 8-pCl phi S-cAMP or insulin-treated cells were identical to those seen in membranes from control cells. Treatment of adipocytes with 8-pCl phi S-cAMP or with insulin did not modify basal rates of cAMP synthesis or alter the ability of adenylate cyclase to be activated by forskolin. The impact of PDE activity on cAMP accumulation was relatively small in membranes from control cells, but treatment of adipocytes with 8-pCl phi S-cAMP or with insulin activated the low Km cAMP PDE and caused a marked decrease in cAMP accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1989

Effects of amlodipine on renal hemodynamics.

Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. This study examined the effects of the novel dihydropyridine amlodipine on the hemodynamic response of the isolated perfused kidney to angiotensin II. Amlodipine completely reversed the angiotensin II-induced decrement in glomerular filtration rate of this model (0.72 +/- 0.15, 0.26 +/- 0.10 and 0.73 +/- 0.12 ml/min/g for control, angiotensin II and angiotensin II plus 0.1 microM amlodipine respectively). In contrast, amlodipine only partially restored renal perfusate flow (35.8 +/- 2.7, 14.7 +/- 1.9 and 23.7 +/- 2.5 ml/min/g for control, angiotensin II and angiotensin II plus amlodipine), thereby increasing filtration fraction. These findings are consistent with previous observations from this laboratory indicating that dihydropyridines predominantly vasodilate preglomerular renal resistance vessels and through this mechanism exert a preferential augmentation of glomerular filtration rate.

Amlodipine↗

PubMed1989

Effect of sodium thiosulfate on the pharmacokinetics and toxicity of cisplatin.

Concurrent administration of sodium thiosulfate (STS) can protect against the nephrotoxic effects of even very-high-dose cisplatin (CDDP) (i.e., 270 mg/m2 given intraperitoneally). The effect of STS on the pharmacology and toxicity of CDDP was investigated in patients receiving at each treatment 90 mg of CDDP/m2 intraperitoneally, with STS given concurrently on alternate cycles by the intravenous route. The patients received a total of 38 courses of therapy, 21 without STS and 17 with STS. STS reduced the total exposure to diethyldithiocarbamate-reactive CDDP for the peritoneal cavity and plasma by 36% and 25%, respectively. When given alone, CDDP caused a statistically significant acute reduction in creatinine clearance levels; this reduction was less evident when STS was given. We conclude that, whereas STS does reduce systemic exposure, the magnitude of this effect was not sufficient to account for the ability of STS to protect against high-dose CDDP.

Cisplatin↗

PubMed1989

Selective intraperitoneal biochemical modulation of methotrexate by dipyridamole.

Dipyridamole increases the toxicity of methotrexate in a concentration-dependent manner. We hypothesized that concurrent intraperitoneal administration of both drugs would result in high peritoneal concentrations with much lower plasma concentrations, permitting a selective increase in the activity of methotrexate against intraperitoneal tumors without enhancing systemic toxicity. Initially, 2.16 mg/m2/d methotrexate and 12 mg/m2/d dipyridamole were delivered together as a constant intraperitoneal infusion for 48 hours. With escalation of chemotherapy, eventually 4.32 mg/m2/d methotrexate was administered for 168 hours. Forty-seven courses were administered to 18 patients. The mean peritoneal to plasma concentration ratios of methotrexate and non-protein bound dipyridamole were 71.6 +/- 34.8 and over 2,300, respectively. Chemical peritonitis was the dose-limiting toxicity. Three patients had some evidence of a response (two with decreasing tumor markers, and the third with a reduction in ascites). We conclude that the drug concentrations are in an appropriate range for selective intraperitoneal biochemical modulation of methotrexate, and that it is feasible to expose tumors confined to the peritoneal cavity to these drugs for long periods of time.

Adult↗

PubMed1987

Phase I/pharmacokinetic study of intraperitoneal cisplatin and etoposide.

We administered cisplatin and etoposide by peritoneal dialysis to 39 patients with i.p. malignancies in order to investigate the toxicity, pharmacokinetics, and clinical activity of this 2-drug combination. All patients received i.v. sodium thiosulfate concurrently with the i.p. chemotherapy. Myelosuppression, nausea, vomiting, and malaise were the primary toxicities encountered. The maximum tolerated dose of etoposide was 350 mg/m2, when administered with a fixed dose of cisplatin, 200 mg/m2. Although the total (free and protein-bound) etoposide exposure for the peritoneal cavity was only 1.5-fold greater than that for the plasma, the free (non-protein bound) etoposide peritoneal exposure was 65-fold greater than the plasma. Tumor regressions were noted in patients with ovarian and pancreatic carcinomas. This study is the first demonstration of the large pharmacokinetic advantage that exists for the i.p. administration of highly protein-bound drugs, and it also documents the clinical activity of i.p. cisplatin and etoposide.

Abdomen↗

PubMed1987

Inhibition by diltiazem of pressure-induced afferent vasoconstriction in the isolated perfused rat kidney.

The renal hemodynamic response to calcium entry blockade depends on the neural, hormonal and physiologic determinants influencing basal renal vascular tone. The effects of perfusion pressure per se on the renal vascular response of the rat kidney to diltiazem were evaluated using normal kidneys and hydronephrotic kidneys perfused extracorporally. In isolated perfused normal kidneys, diltiazem did not alter perfusate flow or glomerular filtration rate (GFR) when administered at a perfusion pressure of 100 mm Hg. In contrast, when diltiazem was administered at a perfusion pressure of 150 mm Hg, the calcium antagonists caused a striking increase in GFR, which was accompanied by an increase in renal perfusate flow. In the isolated perfused hydronephrotic rat kidney, elevation of perfusion pressure was associated with an increase in renal vascular resistance and a reduction in afferent arteriolar diameter. Diltiazem abolished the pressure-induced constriction of afferent arterioles and caused an increase in renal perfusate flow in hydronephrotic kidneys perfused at pressures above 100 mm Hg. These findings suggest that in the setting of increased renal perfusion pressure, diltiazem's effects on GFR are mediated in part by an inhibition of pressure-induced constriction of the afferent arteriole.

Animals↗

PubMed1987

Modification by dihydropyridine-type calcium antagonists of the renal hemodynamic response to vasoconstrictors.

The effects of dihydropyridines on the renal response to vasoconstrictors was assessed using the isolated perfused rat kidney. During norepinephrine-induced vasoconstriction, dihydropyridines preferentially alter glomerular filtration rate and have less of an effect on perfusate flow. Calcium channel antagonists such as nitrendipine and nisoldipine augment glomerular filtration rate, whereas calcium channel agonists depress glomerular filtration rate. A preferential effect on glomerular filtration rate is also observed with the administration of nitrendipine to kidneys during vasoconstriction induced by angiotensin II. In contrast, nitrendipine does not exert a preferential augmentation of glomerular filtration during vasoconstriction mediated by KCl-induced depolarization. These observations are discussed in the context of the cellular mechanisms of dihydropyridines. It is proposed that differing postreceptor processes couple receptor occupation to smooth muscle contraction in afferent and efferent arterioles, and that a selective inhibition of receptor-mediated afferent vasoconstriction may underlie the renal hemodynamic response to dihydropyridines.

Animals↗

PubMed1986

Reversal of renal and smooth muscle actions of the thromboxane mimetic U-44069 by diltiazem.

U-44069 is a stable prostaglandin (PG) H2 analogue and a potent vasoconstrictor. Its in vivo and in vitro actions mimic those of thromboxane A2. We have studied the effects of the calcium antagonist diltiazem upon the vasoconstriction induced by U-44069 using isolated rat aortic smooth muscle and isolated perfused rat kidney (IPRK). The administration of 10(-6)M U-44069 elicited maximally effective contractions in isolated aortic rings and increased 45Ca uptake from a control value of 285 +/- 6 mumol/kg to 344 +/- 8 mumol/kg. Diltiazem reduced U-44069-induced tension development and 45Ca uptake of isolated aortic smooth muscle 73 +/- 2 and 91 +/- 3%, respectively. The dose dependency of each of these effects of diltiazem was similar (EC50 = 369 nM and 334 nM for tension and 45Ca flux, respectively). When administered to the IPRK, 10(-6) M U-44069 caused a 82 +/- 3% decrease in glomerular filtration rate (GFR) and a 80 +/- 4% decrease in filtration fraction but reduced renal perfusate flow (RPF) only 13 +/- 8% (P less than 0.005). Diltiazem completely reversed the actions of U-44069 on the IPRK (EC50 = 288 nM and 323 nM for GFR and RPF, respectively). Diltiazem thus inhibited U-44069-induced tension development and 45Ca uptake by vascular smooth muscle and increased GFR within identical dose ranges. The contractile response of isolated rat glomeruli was also assessed. U-44069 reduced the volume of isolated glomeruli, but this action was neither prevented nor reversed by diltiazem. These results are consistent with the hypothesis that diltiazem increased GFR by inhibiting U-44069-induced Ca influx at preglomerular vessels.

Animals↗

PubMed1985

Effects of diltiazem and manganese renal hemodynamics: studies in the isolated perfused rat kidney.

The effects of the organic calcium antagonist diltiazem (DIL) upon the alterations in renal hemodynamics produced by norepinephrine (NE) were assessed in the isolated perfused rat kidney. In the presence of propranolol, the administration of NE (3 X 10(-7)M) caused sustained reductions in renal perfusate flow (RPF) and glomerular filtration rate (GFR). The administration of 10(-5) M DIL to NE-treated kidneys did not reverse the NE-induced decrease in RPF. In contrast, DIL produced a striking reversal of the NE-induced decrease in GFR. In the absence of NE-treatment, DIL did not alter GFR or RPF. We conclude that NE-induced constriction of major postglomerular resistance vessels of the rat kidney is not inhibited by DIL. In contrast, the DIL-induced increase in GFR of the NE-treated kidneys indicates that the NE-constriction of preglomerular resistance vessels is inhibited by this organic Ca entry blocker. Under identical conditions, manganese, an inorganic calcium entry blocker, reversed the NE-induced reductions in both RPF and GFR, indicating that although both responses depend upon Ca entry, only the latter is sensitive to DIL. These data are, therefore, consistent with the postulate that different regions of the renal vasculature are heterogeneous with regard to the mechanisms mediating NE-induced vasoconstriction.

Animals↗