Biomedical subjects

D Sheikh-Hamad

Publications and source records attributed to D Sheikh-Hamad.

21 records · Page 2Linked to original sources

PubMed1991

Angiotensin II directly increases rabbit renal brush-border membrane sodium transport: presence of local signal transduction system.

In the present study, we have examined the direct actions of angiotensin II (AII) in rabbit renal brush border membrane (BBM) where binding sites for AII exist. Addition of AII (10(-11)-10(-7) M) was found to stimulate 22Na+ uptake by the isolated BBM vesicles directly. All did not affect the Na(+)-dependent BBM glucose uptake, and the effect of AII on BBM 22Na+ uptake was inhibited by amiloride, suggesting the involvement of Na+/H+ exchange mechanism. BBM proton permeability as assessed by acridine orange quenching was not affected by AII, indicating the direct effect of AII on Na+/H+ antiport system. In search of the signal transduction mechanism, it was found that AII activated BBM phospholipase A2 (PLA) and that BBM contains a 42-kDa guanine nucleotide-binding regulatory protein (G-protein) that underwent pertussis toxin (PTX)-catalyzed ADP-ribosylation. Addition of GTP potentiated, while GDP-beta S or PTX abolished, the effects of AII on BBM PLA and 22Na+ uptake, suggesting the involvement of G-protein in AII's actions. On the other hand, inhibition of PLA by mepacrine prevented AII's effect on BBM 22Na+ uptake, and activation of PLA by mellitin or addition of arachidonic acid similarly enhanced BBM 22Na+ uptake, suggesting the role of PLA activation in mediating AII's effect on BBM 22Na+ uptake. In summary, results of the present study show a direct stimulatory effect of AII on BBM Na+/H+ antiport system, and suggest the presence of a local signal transduction system involving G-protein mediated PLA activation.

Angiotensin II↗

PubMed1989

Increased Na+/H+ antiport activity in the renal brush border membrane of SHR.

Defect in renal salt excretion may play an important role in the pathogenesis of hypertension. We examined sodium (Na+) uptake by brush border membrane (BBM) vesicles of young (6 week old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) of the same age. SHR had lower urinary Na+ excretion (223.1 +/- 9.3 vs. 266.3 +/- 3.7 microEq/day/100 g, N = 8, P less than 0.01) and higher systolic blood pressure (98.9 +/- 1.2 vs. 82.9 +/- 1.8 mm Hg, N = 8, P less than 0.01) than WKY. BBM vesicle Na+ uptake, measured by rapid filtration technique, was higher in SHR when compared to WKY (1.44 +/- 0.03 vs. 1.01 +/- 0.06 nmol/mg/5 sec, N = 4, P less than 0.01). This increase in Na+ influx was apparent only in the present of an outward-directed proton (H+) gradient and was abolished by 1 mM amiloride. BBM permeability to H+ as assessed by acridine orange quenching was not different between SHR and WKY. Kinetic analyses of the amiloride-sensitive BBM Na+ uptake revealed a higher Vmax (2.13 +/- 0.27 vs. 0.70 +/- 0.30 nmol/mg/5 sec, N = 4, P less than 0.01) and a higher km for Na+ (3.55 +/- 0.32 vs. 1.23 +/- 0.14 mM, N = 4, P less than 0.05) in SHR. These findings thus demonstrate an intrinsic derangement in BBM Na+ transport in young SHR which is characterized by increased Na+/H+ antiport activity. This alteration in antiport activity is not attributable to changes in membrane permeability to H+, and is characterized by higher Vmax and km.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Prevention of lidocaine-infusion phlebitis by heparin and hydrocortisone.

Previous reports have suggested that infusions of lidocaine (lignocaine) cause a high incidence of phlebitis. We investigated the possibility of reducing this high incidence by the addition of small amounts of heparin or hydrocortisone (or both) to the infusate of lidocaine. One hundred patients with acute myocardial infarction who were to receive a 48-hour prophylactic infusion of lidocaine (2.25 mg/min) were randomized to have one of the following added to their infusate in double-blind fashion: (1) placebo; (2) heparin (4,000 units/24 hr); (3) hydrocortisone (20 mg/24 hr); or (4) heparin and hydrocortisone. After 48 hours the incidence of phlebitis was 94 percent in the control group but only 41 percent in the group receiving heparin and hydrocortisone (p less than 0.005). Had the infusion been stopped after 24 hours, the incidence of phlebitis would have been 56 percent in the group receiving placebo, but only 19 percent in the drug-treated groups (p less than 0.01). We conclude that infusion of lidocaine causes a high incidence of phlebitis which can be markedly reduced by adding heparin or hydrocortisone (or both) to the infusate and limiting the duration of the infusion in a given vein to 24 hours.

Heparin↗