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Biomedical subjects

J G Gerber

Publications and source records attributed to J G Gerber.

At least 91 records · Page 5Linked to original sources
PubMed1982

The effects of a cardioselective (metoprolol) and a nonselective (propranolol) beta-adrenergic blocker on the response to dynamic exercise in normal men.

We compared the effects of a cardioselective beta-adrenergic blocking drug, metoprolol, with a nonselective beta-adrenergic blocker, propranolol, on the response of 10 normal men to dynamic treadmill exercise. The volunteers underwent a standard graded exercise test to exhaustion while receiving placebo; propranolol, 40 mg every 6 hours; propranolol, 80 mg every 6 hours; metoprolol, 50 mg every 6 hours; or metoprolol, 100 mg every 6 hours. The drugs were given in a double-blind fashion for 48 hours before exercise. Five days were allowed between successive drug administrations and the order of drug administration was randomized. Heart rate, arterial pressure, oxygen consumption, minute ventilation and CO2 production were monitored. Plasma drug concentrations were measured at the time of exercise. Judged by plasma levels, propranolol was about three times more potent than metoprolol in attenuating heart rate. Both drugs produced a wide variation in plasma levels after a given oral dose, and both drugs attenuated the systolic blood pressure response to exercise. Neither drug affected diastolic blood pressure or maximum oxygen consumption, maximum minute ventilation or the anaerobic threshold. We conclude that there is no evidence that the cardioselective drug metoprolol is superior to propranolol in terms of the ability to perform or respond to short-term maximal exercise. In addition, the fact that maximal oxygen consumption and the anaerobic threshold were unaffected implies that fatigue during exercise while on beta-adrenergic blocking drugs is not due to an effect of these drugs in limiting blood flow to the exercising extremities.

Adult↗
PubMed1982

Beta adrenergically mediated release of renin in the dog is not confined to either beta-1 or beta-2 adrenoceptors.

The role of the renal beta-1 and beta-2 adrenoceptor subtypes in renin release was evaluated in anesthetized dogs. The renal baroreceptor and macula densa mechanisms of renin release were inhibited by pretreatment with indomethacin (8 mg/kg i.v.). Thus, the beta adrenergic mechanism of renin release was functionally isolated. Intrarenal infusion of isoproterenol at two infusion rates elicited local renal effects and systemic effects at the low and high infusion rates, respectively. Renin secretion was stimulated at both infusion rates. Isoproterenol elicited a significant renin release in the presence of beta-1 adrenoceptor blockade with atenolol and in the presence of selective beta-2 adrenoceptor blockade with IPS-339. In addition, intrarenal infusion of albuterol, a selective beta-2 adrenoceptor agonist, stimulated renin release in the absence and presence of atenolol. These results lead to the conclusion that beta adrenergically mediated release of renin in the dog is not confined to either the beta-1 or beta-2 adrenoceptor subtypes.

Adrenergic beta-Antagonists↗
PubMed1982

Inhibition of acid secretion in isolated canine parietal cells by prostaglandins.

Isolated canine parietal cells were used to evaluate inhibition of acid secretion by both endogenously synthesized and exogenously added prostaglandins (PGs). Uptake of [14C]aminopyrine by the parietal cells was used as an index of acid secretion. The effect of increasing endogenous PG synthesis was determined by incubating arachidonic acid with histamine-stimulated parietal cells. Arachidonic acid (10(-6) and 10(-5) M) was a potent inhibitor of histamine-stimulated acid secretion. This effect of arachidonic acid was totally abolished when the cells were pretreated with 100 microM indomethacin. The effect of exogenous, preformed PGs on histamine-stimulated acid secretion was evaluated by adding PGE2, PGI2, PGF2 alpha or PGD2 to parietal cells. PGE2 was the most potent inhibitor of acid secretion, with a 50% inhibition of maximal acid secretion (ID50) at 7.5 X 10(-8) M. PGI2 and PGF2 alpha also inhibited acid secretion, but at higher concentrations. The ID50 for PGI2 and PGF2 alpha was 10(-5) M. PGD2 was inactive at inhibiting acid secretion. We conclude that both endogenous and exogenous PGs inhibit acid secretion directly at the parietal cells and that PGE2 is most likely the PG produced locally to modulate parietal cell acid secretion.

Animals↗
PubMed1981

Histamine-1 receptors do no directly modulate canine gastric acid secretion.

The role of histamine-1 receptors in modulating gastric acid secretion was evaluated in anesthetized dogs with gastric fistulas. Histamine receptor agonists were infused directly into the gastric artery supplying the fundus to avoid any systemic hemodynamic effects. Two experimental approaches were taken to try to determine whether histamine-1 receptors participate in the control of acid secretion. Firstly, we measured the effect of H1-receptor antagonist, hydroxyzine dihydrochloride, on histamine and dimaprit stimulated acid secretion. Secondly, we measured the effect of H1-receptor agonist on dimaprit stimulated gastric secretion. Although H1-receptor antagonist enhanced stimulated gastric acid secretion to histamine, the antagonist also enhanced stimulated gastric acid secretion to dimaprit (H2-agonist), suggesting that the enhanced gastric acid secretion after administration of H1-receptor antagonist is not because of the inhibition of histamine receptor at the gastric fundus. In addition, two doses of H1-receptor agonist infused into the gastric fundus had no effect on dimaprit stimulated gastric acid secretion. These data suggest that H1-receptors do not modulate gastric acid secretion at the level of the gastric fundus in the dog.

Animals↗
PubMed1981

Interaction between furosemide-induced renal vasodilation and the prostaglandin system.

The effect of intravenous furosemide, 5 mg/kg, on renal hemodynamics as it relates to the prostaglandin cascade was examined in dogs. In 11 dogs the vasculature to the kidney was isolated and a femoral to renal arterial and a renal to femoral venous shunt was performed. With the use of a protein-free salt solution to perfuse the kidney for 3 minutes, the renal cortex was enriched with tritiated arachidonic acid. After blood perfusion to the kidney was re-established, the renal effluent radioactivity was followed before and after furosemide administration. Furosemide produced two types of response. In six dogs there was renal vasodilation, diuresis, and a three and one-half fold increase in renal venous radioactivity. In five dogs that were in renal failure, furosemide administration caused no change in renal effluent radioactivity. On thin-layer chromatography most of the released radioactivity by the kidney after furosemide administration traveled as arachidonic acid. In a separate seven dogs, we measured the total unesterified arachidonic acid concentration in the plasma before and after furosemide by the use of gas chromatography-flame ionization. Even though in these dogs furosemide caused a significant increase in renal blood flow and diuresis, renal venous plasma levels of arachidonic acid were unaltered. Our data suggest that furosemide causes a release of arachidonic acid from the kidney from a small pool at fast turnover lipid stores and that the stimulus for arachidonic acid release after furosemide depends on a intra-renal mechanism whereby the diuresis is coupled to the increase in renal blood flow.

Animals↗
PubMed1981

Control of canine renin release: macula densa requires prostaglandin synthesis.

1. The macula densa mechanism of renin release was functionally isolated in uninephrectomized, anaesthetized dogs by producing renal denervation, beta-adrenoceptor blockade, and maximum renal vasodilation with an infusion of papaverine into the renal artery. 2. A suprarenal aortic clamp was adjusted to reduce renal perfusion pressure by 50% which resulted in a 90% reduction in urinary sodium excretion and a two to threefold increase in plasma renin activity within 10 min. 3. Indomethacin (8 mg/kg) or meclofenamic acid (10 mg/kg) inhibited the rise plasma renin activity produced by the decrease in renal perfusion pressure in this model, although a comparable decrease in urinary sodium excretion was achieved. 4. We conclude that the macula densa mechanism of renin release is blocked by inhibition of prostaglandin synthesis.

Animals↗
PubMed1981

Release of vasodilator prostaglandin, PGI2, from isolated rat lung during vasoconstriction.

Prostaglandins are generated by the lungs and released into the circulation. Since inhibitors of prostaglandin synthesis enhance hypoxic pulmonary vasoconstriction, we wondered whether vasodilator prostacyclin was synthesized by the lungs in response to vasoconstriction. To test this hypothesis, we measured vasoconstriction induced by angiotensin II in isolated rat lungs before and after inhibition of prostaglandin synthetase. We found that sodium meclofenamate enhanced and prostacyclin and its precursor arachidonate abolished pulmonary vasoconstriction. In lungs labeled with 14C-arachidonate, effluent radioactivity increased after angiotensin II-induced vasoconstriction. Hypoxic vasoconstriction, but not hypoxia per se, caused an increase in lung effluent radioactivity. Chromatographic analysis of lung effluent showed that 6-keto-prostaglandin F1 alpha was the major arachidonic acid metabolite released during pulmonary vasoconstriction. We concluded that prostacyclin is produced by the lungs in response to vasoconstriction. Hypoxia per se seems not to be the adequate stimulus for enhanced lung prostacyclin formation. Lung prostacyclin may protect the pulmonary circulation against excessive vasoconstriction.

Angiotensin II↗
PubMed1981

Prostacyclin produced by the pregnant uterus in the dog may act as a circulating vasodepressor substance.

Uterine production of PGI2 (prostacyclin) was quantitated in late pregnant dogs to evaluate if PGI2 could act as circulating vasodepressor substance in pregnancy. In five anesthetized, laparotomized dogs, the uterine venous plasma concentration of 6-keto PGF1 alpha (the in vitro hydrolysis product of PGI2) was 6.7 +/- 1.9 ng/ml and the arterial plasma concentration was 2.6 +/0 0.8 ng/ml. In four nonpregnant female dogs the arterial plasma concentration of 6-keto PGF1 alpha was consistently below 0.2 ng/ml. In eight pregnant dogs we also evaluated the ability of the pregnant uterus to inactivate PGI2 by comparing the hypotensive response to increasing doses of PGI2 infused into the uterine artery to the hypotensive response to increasing doses of PGI2 infused into the inferior vena cava. In addition, the effect of PGI2 infused into the uterine artery on uterine blood flow and intraamniotic fluid pressure was evaluated. The dose-response curves of intrauterine and intravenous PGI2 in causing systemic hypotension were identical suggesting that the pregnant uterus does not inactivate infused PGI2. Intrauterine PGI2 had no consistent effect on uterine hemodynamics although it did increase intraamniotic fluid pressure significantly. These data demonstrate that the pregnant uterus has the capacity to produce large quantities of PGI2 which is not inactivated in the uterus and therefore can appear in the arterial blood to exert a systemic vasodepressor effect.

Animals↗
PubMed1981

Alpha adrenergic-mediated renin release is prostaglandin-dependent.

The contribution of the alpha adrenergic receptor activation to the sympathetic mediated renin release was examined by utilizing intrarenal phenylephrine infusion in beta adrenergically blocked anesthetized mongrel dogs. Increasing doses of intrarenal phenylephrine resulted in a dose-dependent decrease in renal blood flow, a dose-dependent decrease in urinary excretion of sodium and a stimulation of renal renin release which was not dose-dependent. The effect of intrarenal phenylephrine on renin release was totally abolished by pretreating the dogs with indomethacin, even though neither the vasoconstriction nor the decrement in urinary sodium excretion was altered by the drug. In addition, intrarenal phenylephrine did not elicit renal renin release in dogs with kidneys that were rendered nonfiltering. These data are consistent with the hypothesis that exogenous renal alpha adrenergic stimulation in the dog contributes to renin release through the prostaglandin system and that the stimulation of the macula densa mechanism is responsible for the major effect of phenylephrine on renin release.

Animals↗
PubMed1980

Prostaglandin production by intact isolated gastric parietal cells.

An enriched population of isolated gastric parietal cells was obtained from canine gastric mucosa. Parietal cells incubated with [14C]arachidonic acid produced radiolabelled PGF2 alpha, PGE2, PGD2 and 6-keto PGF1 alpha (acid hydrolysis product of PGI2). The prostaglandin synthesis was inhibited by indomethacin. Prostaglandin production, as measured by gas chromatography-mass spectrometry demonstrated that PGF2 alpha was produced in the highest quantity followed by PGE2 and 6-keto PGF 1 alpha. This demonstrates that isolated prietal cells are capable of producing prostaglandins. Since prostaglandins have a potent effect on gastric acid secretion, local prostaglandin synthesis could modulate parietal cell function.

Animals↗
PubMed1980

Furosemide-induced vasodilation: importance of the state of hydration and filtration.

The circumstances under which furosemide increases renal blood flow was examined in mongrel dogs as it may relate to a tubuloglomerular feedback mechanism. Two maneuvers, desoxycorticosterone (DOCA) plus salt treatment and inhibition of tubular fluid flow, were used in the dogs to evaluate the renal vascular effects of furosemide because these maneuvers have been reported to blunt the tubuloglomerular feedback in micropuncture studies. In addition, we also used two structurally different nonsteroidal antiinflammatory drugs to assess the importance of prostaglandins to achieve furosemide's renal vasodilatation. Furosemide (5 mg/kg, i.v.) increased renal blood flow in volume-depleted animals from a baseline flow of 141 +/- 28 ml/min to a maximum of 176 +/- 35 ml/min at 6 min after furosemide administration. If the animals were pretreated with a high-salt diet and i.m. DOCA for 5 days, furosemide administration produced no renal vascular effects but still caused a large diuresis, and these dogs still had a responsive renal vascular bed to infused prostaglandin E2. In addition, kidneys rendered non-filtering in volume-depleted animals had no renal vascular response to furosemide. Volume-depleted animals, pretreated with either indomethacin or sodium meclofenamate, did not have a renal vascular response to furosemide although they did have a diuretic response and a responsive renal vasculature to prostaglandin E2. From our data, we hypothesize that the renal vascular response to furosemide is secondary to a tubular mechanism mediated by a vasodilatory prostaglandin. Because furosemide has been shown to disrupt the tubuloglomerular feedback mechanism, and the two maneuvers, DOCA plus salt treatment and lack of filtration, blunt the tubuloglomerular feedback response as well as inhibit the renal vascular response to furosemide, we further hypothesize that furosemide-induced renal vasodilation may be secondary to the disruption of an active tubuloglomerular feedback mechanism.

Animals↗
PubMed1980

Prazosin does not alter canine renin release in response to systemic hypotension or intrarenal isoprenaline and prostaglandin I2 infusion.

1. The effect of a hypotensive dose of intravenous prazosin (0.2 mg/kg) on heart rate and plasma renin activity was evaluated in anaesthetized mongrel dogs pretreated with indomethacin. 2. The effect of prazosin on the renin release elicited by the beta-adrenoceptor agonist isoprenaline and by prostaglandin I2 was also evaluated. 3. Prazosin administration was associated with a significant increase in heart rate and increase in plasma renin activity. 4. Prazosin did not interfere with the increase in plasma renin activity in response to either isoprenaline or prostaglandin I2. 5. We conclude that prazosin is not a unique peripheral vasodilator since hypotensive doses are associated with an increase in heart rate and plasma renin activity. In addition, prazosin does not inhibit the release of renin induced by either isoprenaline or prostaglandin I2.

Animals↗