PubMed Health⌕ Search

Biomedical subjects

J G Gerber

Publications and source records attributed to J G Gerber.

At least 55 records · Page 3Linked to original sources
PubMed1988

Age does not alter human vascular and nonvascular beta 2-adrenergic responses to isoproterenol.

beta-Adrenoceptor-mediated functions appear to diminish with aging, but the exact scope of these changes is unknown, because most studies have been limited to beta 1-adrenergic cardiac phenomena. To evaluate both a vascular and a nonvascular beta 2-adrenergic response in the aged, we have studied 12 healthy elderly and 12 healthy young subjects infused with increasing doses of isoproterenol and compared the change in peripheral vascular resistance, measured by venous occlusion plethysmography, and insulin release. In both groups vascular resistance fell and insulin concentrations increased. These changes were equivalent in both groups, and we therefore infer no significant decline in either of these beta 2-adrenergic functions in the elderly.

Adult↗
PubMed1988

Comparison between the effects of aging on antagonist and agonist interactions with beta-adrenergic receptors on human mononuclear and polymorphonuclear leukocyte membranes.

Age-related differences in the binding properties of beta-adrenergic receptors on lymphocyte membranes isolated from healthy individuals have been reported. The purpose of the present studies was to determine whether or not beta receptors on polymorphonuclear leukocyte (PMN) membranes showed similar age-related changes. Plasma Percoll gradients were used to isolate PMN and mononuclear leukocyte (MN) cells from blood drawn in the supine position from young (25-34 years) and elderly (60-76 years) healthy volunteers. Both blood pressures and plasma norepinephrine levels were significantly elevated in the elderly subjects. Saturation analysis with [125I]-(-) iodopindolol (IPIN) showed a 2.5-fold higher density of beta 2 receptors on the MN, but not PMN, membranes from the elderly. Neither the affinities of the receptor for IPIN or the agonist isoproterenol, nor the GTP-induced shift in agonist affinity, differed with subject age in either cell type. These results suggest that subpopulations of MN cells on which beta-adrenergic receptors are localized may increase in the elderly and that it is important to measure receptor properties on a more homogeneous leukocyte population such as PMN cells or subpopulations of MN cells as a function of aging.

Adrenergic beta-Agonists↗
PubMed1988

Propranolol increases prostacyclin synthesis in patients with essential hypertension.

We tested the hypothesis that vascular prostacyclin synthesis is increased by propranolol and could account for some of the drug's antihypertensive effect. We studied 10 white patients with mild essential hypertension in a randomized, double-blind design to assess the effects of indomethacin with or without the addition of propranolol on blood pressure and vascular prostacyclin biosynthesis, as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha), F1 alpha (PGF1 alpha), measured by gas chromatography-mass spectrometry. Seven patients responded to propranolol with a lowering of mean arterial blood pressure in both supine and upright postures. The fall in mean arterial blood pressure (-14.1 +/- 2.1 mm Hg sitting; -17.4 +/- 1.7 mm Hg supine) with propranolol alone was significantly greater than that produced when propranolol was given to patients receiving indomethacin (-7.8 +/- 1.9 mm Hg sitting; -7.7 +/- 3.0 mm Hg supine). Our drug-responsive patients demonstrated a significantly lower excretion rate of 2,3-dinor-6-keto-PGF1 alpha than was found in an age and sex-matched group of normal volunteers. With propranolol treatment, drug-responsive patients showed a significant increase in the excretion of 2,3-dinor-6-keto-PGF1 alpha, such that the mean excretion was not significantly different from that in normal volunteers. Indomethacin caused a significant rise in mean arterial blood pressure and a significant fall in 2,3-dinor-6-keto-PGF1 alpha excretion, and it blocked the rise in urinary 2,3-dinor-6-keto-PGF1 alpha associated with propranolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Endogenous adenosine modulates gastric acid secretion to histamine in canine parietal cells.

We have recently demonstrated the presence of A1 adenosine receptors on canine parietal cells which are involved in the inhibition of histamine-stimulated acid secretion. In order to demonstrate the importance of endogenously generated adenosine on acid secretion we examined the effect of compounds that either increase or decrease the availability of adenosine to the A1 receptor on histamine-stimulated parietal cell aminopyrine (AP) accumulation. Inclusion of 10 microM 8-phenyltheophylline, an adenosine receptor antagonist, with the cells resulted in a 35 +/- 12% and 31 +/- 9% increase in parietal cell AP accumulation at histamine concentrations of 1 microM and 10 microM, respectively. The effect of 8-phenyltheophylline was specific to histamine in that it did not affect carbachol-stimulated AP accumulation or dibutyryl cyclic AMP-stimulated AP accumulation. Inclusion of 1 microM dipyridamole, an inhibitor of adenosine transport, resulted in a 34 +/- 6% and 31 +/- 5% decrease in parietal cell AP accumulation at histamine concentrations of 1 microM and 10 microM, respectively. Again the effect of dipyridamole was specific to histamine in that it did not affect either carbachol- or dibutyryl cyclic AMP-stimulated AP accumulation. The addition of adenosine deaminase, 500 mU/ml, resulted in an enhanced histamine-stimulated AP accumulation at all the histamine concentrations. The effect was specific to histamine because the enzyme had no effect on either carbachol- or dibutyryl cyclic AMP-stimulated AP uptake. Our present data suggest that endogenous adenosine generated by the gastric cells can interact with parietal cell adenosine receptors to modulate acid secretion to histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1988

Local vasodilator effect of platelet activating factor in the gastric, mesenteric and femoral arteries of the dog.

Platelet activating factor (PAF) has been postulated to have vascular effects that contribute to gastrointestinal ulceration and necrosis produced during endotoxin shock. To evaluate the regional arterial effects of PAF and its interaction with cyclooxygenase metabolites of arachidonic acid, we infused increasing doses of PAF (calculated to achieve an initial plasma concentration of 2 X 10(-9), 10(-8), 5 X 10(-8) M) into the gastric, mesenteric and femoral arteries in the presence or absence of indomethacin (5 mg/kg) in anesthetized dogs. During a 5-min infusion of PAF, regional resistances in the gastric, mesenteric and femoral arterial circulations decreased transiently and dose dependently in the initial phase (minute 1 and 2) by 71, 65 and 64%, respectively. In the late phase (minute 3-5), the arterial resistance returned gradually toward base line in the gastric and mesenteric circulations but remained reduced in the femoral arterial circulation. In the vehicle-treated group, the effect of PAF was reproducible. In the indomethacin-treated group, the initial vasodilator response to PAF was not altered in any of the arterial circulations, but in the late phase, the return of arterial resistance toward base line in the gastric and mesenteric circulations was attenuated by indomethacin (P less than .05). In contrast, in the femoral circulation, indomethacin enhanced the return of the arterial resistance (P less than .05) toward base line.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The balance between vascular alpha- and beta-adrenoceptors is not changed in the elderly.

It has been suggested that beta-adrenoceptor-mediated functions are diminished with aging and that these responses are reduced to a greater extent than are alpha-adrenoceptor-mediated responses. The resulting imbalance in the elderly may produce an increased vascular resistance from the unopposed alpha-adrenoceptor stimulation in the peripheral vasculature. To evaluate this hypothesis, we studied 12 healthy elderly and 12 healthy young subjects during a graded infusion of epinephrine and compared blood pressure response, vascular resistance, and calf blood flow as determined by venous occlusion plethysmography. In both groups, heart rate increased, blood flow to the leg increased, and vascular resistance fell in response to epinephrine infusion, but in the elderly the systolic blood pressure failed to rise as it did in the young subjects. From these data we conclude that the overall vascular response to epinephrine does not change with age and that the balance between beta-adrenoceptor-mediated vasodilation and alpha-adrenoceptor-mediated vasoconstriction is therefore unchanged in the elderly.

Adult↗
PubMed1987

L-platelet activating factor induces changes on renal vascular resistance, vascular reactivity, and renin release in the isolated perfused rat kidney.

Rat kidneys were isolated and perfused with a modified Krebs-Henseleit buffer containing 4% albumin. Perfusate recirculated except during L-platelet activating factor (L-PAF), angiotensin II (ang II), and norepinephrine (NE) infusions. L-PAF caused a dose-dependent decrease in renovascular resistance (RVR): -6 +/- 3% at 10(-9)M, -12 +/- 6% at 10(-8)M, -18 +/- 3% at 10(-7) and -20 +/- 7% at 10(-6)M. L-PAF increased immunoreactive PGE (iPGE) and thromboxane (iTXB) release into the venous effluent from 2.4 +/- 0.2 to 3.9 +/- 0.4 ng/min (p less than 0.05) and from 2.1 +/- 0.4 to 3.5 +/- 0.5 ng/min (p less than 0.05), respectively. Vasodilation by L-PAF (10(-7) M) in the presence of indomethacin (INDO) (5 microM) was enhanced compared to the non-INDO response (RVR change: L-PAF = -18 +/- 3% vs. L-PAF = -26 +/- 3%; p less than 0.05). As a control for specificity, the was infused at 10(-9) M, 10(-8) M, and 10(-7) M. None of these concentrations changed renal vascular resistance. To study the vascular receptor responsible for L-PAF-induced vasodilation, dose-response curves to NE and ang II were established with and without L-PAF (10(-7) M). The NE dose-response curve was unchanged by L-PAF, whereas the ang II dose-response curve was shifted to the right by one order of magnitude. In kidneys pretreated with INDO (5 microM), the L-PAF-induced shift of the ang II dose-response relation was increased to 2-3 orders of magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1987

Histamine release in vivo by pentagastrin from the canine stomach.

The effect of intragastric arterial infusion of pentagastrin on gastric histamine release was evaluated in mongrel dogs in vivo. Histamine secretory rates were evaluated by measuring the arterial and gastric venous plasma histamine concentrations at 0, 5, 10, 15 and 20 min into pentagastrin infusions, and gastric blood flow was continuously monitored. Histamine secretory rates were calculated by subtracting the arterial from the venous histamine concentrations and multiplying the difference by gastric plasma flow. Two separate 20-min infusions of pentagastrin, separated by 60 min, resulted in a peak of histamine release in 5 to 10 min that returned to base line within 20 min. During the first infusion, histamine release peaked at 179 ng/min, whereas, during the second infusion, histamine peaked at 125 ng/ml. The increase in gastric blood flow to pentagastrin correlated with the increases in histamine release. Somatostatin infused into the gastric artery to attain a concentration of 10 nM, a concentration that results in the inhibition of gastric acid secretion, abolished the gastric histamine release to pentagastrin. In addition, somatostatin also attenuated the gastric vasodilation to pentagastrin. Our data indicate that, in the in vivo dog model, pentagastrin can cause a pulsed release of gastric histamine, and somatostatin inhibits this release of histamine.

Animals↗
PubMed1987

Prostaglandin E2 and [14C]arachidonic acid release by carbachol in the isolated canine parietal cell.

Parietal cells have the capacity to synthesize prostaglandins (PGs) and these PGs have a significant effect on parietal cell acid secretion. We examined the stimuli responsible for the control of PG production by parietal cells. Two approaches were utilized. One consisted of measuring PGE2 concentration in the incubation media containing dispersed canine parietal cells stimulated with increasing concentrations of carbachol, histamine plus a phosphodiesterase inhibitor and pentagastrin. PGE2 was measured by radioimmunoassay. The other consisted of measuring the release of radioactive arachidonic acid by parietal cells prelabeled with [4C]arachidonic acid to increasing concentrations of the secretagogues. Both techniques gave very similar results. Only carbachol stimulated the release of PGE2 as well as [14C]arachidonic acid into the incubation media. The increase in PGE2 release was from a base line of 44.3 +/- 10.8 pg/ml to 51.0 +/- 11.7, 55.2 +/- 11.1 and 69.3 +/- 14.3 pg/ml at carbachol concentrations of 10(-6), 10(-5) and 10(-4) M, respectively. In prelabeled cells, carbachol stimulated 1072 +/- 141 and 1264 +/- 155 cpm/ml above basal at concentrations of 10(-5) and 10(-4) M, respectively. Neither histamine nor pentagastrin stimulated PGE2 or [14C]arachidonic acid release significantly at any concentration. The effect of carbachol on the release of [14C]arachidonic acid was blocked by atropine and the exclusion of calcium from the incubation media. Our data suggest that the cholinergic tone to the stomach with subsequent interaction of acetylcholine with muscarinic receptors determines the amount of PG production by the parietal cells. Prostaglandins may then modulate acid secretion by limiting the combined, potentiated effects of the secretagogues.

Animals↗
PubMed1986

Somatostatin's ability to inhibit gastric acid is not prostaglandin-mediated in the dog.

The role of prostaglandins in the effect of somatostatin to inhibit cholinergically stimulated gastric acid output was examined in gastric fistula dogs. Methacholine stimulation of gastric acid output to a maximum of 810 +/- 423 mu eq of [H+] per 15 min was inhibited by 10 nM somatostatin to the same extent either in the presence and/or the absence of indomethacin. In contrast, histamine-induced acid secretion was stimulated weakly by 10 nM somatostatin. Our data do not support a role for prostaglandins in somatostatin's action to inhibit cholinergically stimulated acid secretion.

Animals↗
PubMed1986

Beta-adrenergic receptors in the elderly are not less sensitive to timolol.

The elderly have been reported to be less sensitive to the beta-adrenergic blocking effect of propranolol. However, propranolol is a racemate, and age-related changes in stereoselective metabolism or protein binding could confound interpretation of the data. To avoid these problems, we studied timolol in 12 young and 12 elderly healthy subjects. The dose of isoproterenol required for a heart rate increase of 25 bpm (I25) was determined before and 2 hours after an oral 10 mg dose of timolol. A dose ratio (DR) was calculated for each subject as the I25 after timolol/I25 before timolol. The binding constant for timolol binding to the receptor was calculated as the plasma timolol concentration divided by (DR-1). The I25 for the elderly group was significantly greater than the I25 for the young group, but the timolol binding constant was the same for both groups. We conclude that, although the elderly are less sensitive to isoproterenol, they are not less sensitive to timolol, and thus our data do not implicate a change in the interaction of beta-adrenoceptors with antagonists.

Adult↗
PubMed1986

Renal vasoconstrictor response to hypertonic saline in the dog: effects of prostaglandins, indomethacin and theophylline.

The role of prostaglandins in the mechanism of the tubuloglomerular feed-back was examined in the anaesthetized dog using the infusion of hypertonic saline to increase renal plasma sodium concentration by 30 mmol/l as the stimulus to activate the tubuloglomerular feed-back. Two sequential infusions of hypertonic saline into the renal artery for 10 min separated by 90 min resulted in equivalent reductions in renal blood flow (264 +/- 32 to 174 +/- 20 ml/min first time; 280 +/- 29 to 200 +/- 15 ml/min second time). Administration of indomethacin, 8 mg/kg, between the two infusions did not alter the renovascular response to hypertonic saline (319 +/- 26 to 226 +/- 35 ml/min vs. 288 +/- 32 to 202 +/- 24 ml/min). Infusion of either prostaglandin E2 (PGE2) or prostaglandin I2 (PGI2) during the second hypertonic saline infusion period also resulted in no change in the renovascular response (251 +/- 37 to 141 +/- 31 ml/min vs. 297 +/- 53 to 184 +/- 51 ml/min; and 223 +/- 31 to 162 +/- 35 ml/min vs. 254 +/- 33 to 186 +/- 39 ml/min, respectively). Intrarenal theophylline, to a concentration of 40 micrograms/ml, however, totally abolished the renovascular response to hypertonic saline (279 +/- 20 to 209 +/- 13 ml/min control vs. 390 +/- 26 to 402 +/- 17 ml/min during theophylline). The systemic hypertensive response during the infusion of hypertonic saline was unaltered by indomethacin or prostaglandins but was totally abolished by theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Increased PGE2 excretion by dDAVP in humans depends on state of hydration.

The relationship of renal prostaglandin E2 (PGE2) excretion (UPGEV) to water deprivation, water diuresis, and subsequent antidiuresis by 1-desamino-8-D-arginine vasopressin (dDAVP) was studied in female volunteers. After 16 h of water deprivation, the subjects began a sustained water diuresis for 8 h. This diuresis caused a transient twofold rise in UPGEV at 2 h (P less than 0.05), which then fell back to or below baseline levels. dDAVP given during the water diuresis caused a transient rise of UPGEV as urine volume decreased and plasma osmolality fell from 277 +/- 1.5 to 271 +/- 2 mosmol/kg (P less than 0.01). Another group of subjects had the water diuresis discontinued after 4 h with dDAVP given at the 5th h when urine volume was decreasing and urine osmolality was increasing. In this setting dDAVP did not produce as great a fall in plasma osmolality nor did it increase UPGEV. These data indicate that renal prostaglandin synthesis (as determined by UPGEV) is increased transiently by an acute water load; dDAVP given during continued water ingestion results in a fall in plasma osmolality and increased PGE excretion; however, dDAVP does not increase UPGEV during normal hydration; and UPGEV is independent of changes in urine flow. These findings imply that renal prostaglandins may have a functional role in humans to inhibit the hydroosmotic actions of antidiuretic hormone, and thus hasten the excretion of a water load, and to prevent overhydration when inappropriate antidiuresis occurs. However, there is no evidence that the stimulus for prostaglandin production is dDAVP per se.

Adult↗
PubMed1986

Hemodynamic effects of platelet activating factor in the dog kidney in vivo.

The effect of platelet activating factor (PAF) on renal hemodynamics and function was examined in anesthetized dogs. The infusion of PAF into the renal artery at 5, 10, and 20 ng X min-1 X kg-1 body weight resulted in dose-dependent reductions in renal blood flow, glomerular filtration rate, urine volume, and urinary sodium excretion, whereas the infusion of vehicle alone in the contralateral kidney did not result in significant changes in these parameters. The maximum decrease expressed as the percent change from baseline was 22.2 +/- 1.7% for renal blood flow, 50.8 +/- 11% for glomerular filtration rate, 67.3 +/- 4.2% for urine volume, and 69.0 +/- 8.5% for urinary sodium excretion, respectively. These renal effects were not accompanied by significant alterations in systemic arterial blood pressure and heart rate. Pretreatment with indomethacin to block prostaglandin synthesis enhanced the effect of PAF on kidney function. Our data demonstrate that, unlike the rat kidney, intrarenal PAF infusion into the intact dog results in vasoconstriction and serve reduction in glomerular filtration rate.

Animals↗
PubMed1986

Effects of pindolol and propranolol on beta adrenergic receptors on human lymphocytes.

The cardiovascular supersensitivity observed after discontinuation of administration of beta adrenergic receptor antagonists may be explained by an increase in the density of beta adrenergic receptors. Thus, a change in the density of receptors has been observed in human lymphocytes after administration of propranolol (Aarons et al., 1980). The effects of pindolol, a beta adrenergic receptor antagonist with intrinsic sympathomimetic activity, were compared with those of propranolol or placebo. Pindolol (10 mg q.i.d.), propranolol (40 mg q.i.d.) or placebo were administered to 12 subjects for 8 days. The density of beta adrenergic receptors was determined by Scatchard analysis of the specific binding of [125I]iodopindolol on membranes prepared from human lymphocytes. Administration of pindolol resulted in a 30 to 50% decrease in the density of beta adrenergic receptors. This decrease was apparent within 1 day of beginning pindolol administration and it persisted for at least 8 days after discontinuation of drug administration. The reversibility of the decrease in receptors observed after pindolol administration was studied in 27 subjects given propranolol, pindolol or placebo for 4 days in a double-blind cross-over trial. Propranolol consistently induced a small increase in the density of beta adrenergic receptors. The density of receptors returned to predrug values within 2 days after discontinuation of propranolol administration. Pindolol induced a 30 to 50% decrease in the density of receptors which, as observed previously, persisted for at least 10 days after discontinuation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

A dual effect of nonsteroidal anti-inflammatory drugs on renal water handling in humans.

The role of renal prostaglandins (PGs) in the induction and maintenance of a sustained water diuresis was studied by using two different nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and meclofenamate given either before or during the diuresis. Urinary PGE2 excretion increased with the initiation of a water diuresis (from 2.5 +/- 0.7 to 6.1 +/- 1 pg/kg/min during the 2nd hr, P less than .01) but then fell back to control levels when water diuresis was established. Pretreatment with NSAIDs abolished the initial increase in PGE excretion and delayed the onset of the water diuresis so that 1 hr after the initiation of the diuresis, the urine osmolality in the control subjects was 205 +/- 50 mosm/kg as compared with 440 +/- 55 mosm/kg (P less than .05) for the NSAID-treated subjects. In contrast, the urine osmolality did not change when subjects were given the NSAIDs 5 hr after the onset of the water diuresis. However, the NSAIDs did decrease urine volume and free water clearance for as long as the urinary PG excretion was suppressed, regardless of when the drugs were given. This action of the NSAIDs to decrease the urine volume and free water clearance was due to a decrease in delivery of water and solute to the diluting segments of the nephron. These data imply that the transient increase in urinary PGE excretion occurring at the onset of a water diuresis has functional significance, as NSAIDs block the increase in PG synthesis and also interfere with the onset of a water diuresis by delaying the attainment of a maximally dilute urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents↗
PubMed1985

Sulindac is not renal sparing in man.

We investigated the claimed renal-sparing effect of the cyclooxygenase inhibitor sulindac. Fifteen normal women following a diet of 50 mEq salt a day were randomly assigned to 5 days of either placebo, sulindac, 200 mg b.i.d., or indomethacin, 25 mg q.i.d., after first serving as their own controls. Renal effects were assessed by the excretion rate of prostaglandin (PG) E2 (an index of renal PG synthesis), sodium balance, plasma renin activity (PRA), and the response to furosemide. Systemic effects were assessed by collagen-induced platelet aggregation and thromboxane B2 formation and by the urinary excretion of a systemically formed metabolite of PGF2 alpha (PGF-M). Both sulindac and indomethacin resulted in a positive sodium balance and a reduction in 24-hour urinary PGE2 excretion (range -49% to -86%). Basal PRA was decreased by indomethacin only, but the increases in PRA and in urinary PGE2 excretion in response to furosemide were inhibited by both sulindac and indomethacin. Sulindac reduced the natriuresis induced by furosemide, and indomethacin reduced the rise in inulin clearance after furosemide. Thus the two nonsteroidal anti-inflammatory drugs had similar effects on the kidney. Indomethacin had a greater effect than sulindac on the inhibition of collagen-induced platelet aggregation and thromboxane synthesis and the two drugs had equivalent effects on the reduction of PGF-M excretion. Peak plasma drug concentration of indomethacin (1.9 +/- 0.4 microgram/ml) and sulindac sulfide (7.7 +/- 1.9 microgram/ml) were those associated with clinical efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗