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Biomedical subjects

J W Strandhoy

Publications and source records attributed to J W Strandhoy.

At least 37 records · Page 2Linked to original sources
PubMed1986

Comparison of the renal effects of indoramin and prazosin.

Indoramin and prazosin are both potent and selective alpha 1 adrenoceptor antagonists. Indoramin has been reported to decrease baroreceptor sensitivity, whereas prazosin has been reported to increase it. The current studies examined the relative potencies of the two drugs in inhibiting the renal vascular alpha 1 adrenoceptor and also the renal and cardiovascular effects of these agents. The drugs were infused intravenously at rates in which they equally antagonized alpha 1-receptors. Indoramin decreased blood pressure by as much as 29 mm Hg with the doses tested and also significantly (p less than 0.05) reduced heart rate. Sodium, potassium, and water excretion, and glomerular filtration rate (GFR) were unchanged. Prazosin tended to reduce blood pressure, but the 11 mm Hg fall was not statistically significant. Heart rate increased significantly (p less than 0.05). Sodium, potassium, and water excretion decreased, with a return toward control values of urine flow but not sodium excretion with higher doses. The GFR was unchanged. The results of this study indicate that neural and endocrine factors modify direct drug effects and that indoramin and prazosin administered acutely differ in the recruitment of these reflexes.

Animals↗
PubMed1985

Role of alpha-2 receptors in the regulation of renal function.

Postsynaptic binding sites for alpha 1 and alpha 2 adrenoceptor ligands are found in abundance in the renal cortex of several species, with reports of 2-3 times as many alpha 2 as alpha 1 sites. These alpha adrenoceptor subtypes can potentially influence salt and water excretion through both vascular and tubular effects. Renal vascular resistance in dogs is increased by both alpha adrenoceptor subtype agonists but alpha 1 agonists are more potent. In rats, alpha 2, agonists have almost no effect on the renal circulation whereas alpha 1 agonists are capable of intense renal vasoconstriction. The mechanisms by which alpha 2 agonists increase glomerular filtration rate are not yet clear and may involve the secondary release of hormones affecting glomerular dynamics and permeability. Thus, an abundance of alpha 2 adrenoceptor binding sites in whole cortical homogenate of rat kidneys with little demonstrable vascular effect of alpha 2 agonist suggests that the preponderance of these receptors lies instead on the tubular epithelium. Alpha-1 adrenoceptors are probably responsible for the increased Na reabsorption from the proximal tubule and the anti-natriuresis following low level renal nerve stimulation. In contrast, an alpha 2 agonist such as guanabenz produces a diuresis by reducing the release of vasopressin and by antagonizing its hydrosmotic effect on the nephron, and a modest natriuresis by decreasing medullary interstitial osmolality and reducing passive Na reabsorption.

Adrenergic alpha-Agonists↗
PubMed1984

Effect of guanabenz withdrawal on blood pressure and plasma catecholamines.

Previous studies provide conflicting conclusions concerning the consequences of abrupt withdrawal of guanabenz therapy for essential hypertension. In the present study, 10 patients were treated for mild to moderate essential hypertension for 12 weeks, following which the drug was abruptly withdrawn. Blood pressure, pulse rate, and plasma catecholamine levels were obtained before, at 4 and 12 weeks after starting therapy, and 48-96 h and 4 and 8 weeks post-therapy. At the end of 12 weeks of therapy, the mean dose of guanabenz was 22.2 +/- 4.4 mg/day (range, 16-48 mg/day) and supine blood pressure was 140 +/- 5.5/88 +/- 2.4 mm Hg. Two to 4 days after drug withdrawal, supine and standing diastolic blood pressure remained significantly reduced compared to control (p less than 0.01). Standing systolic blood pressure also remained significantly reduced compared to control (p less than 0.01). Mean plasma catecholamine level was less than baseline after 4 weeks of therapy, but the change was not significant. No increase in plasma catecholamine concentration was observed at any time during the withdrawal period. No patient had symptoms of sweating, nervousness, palpitations, or insomnia after guanabenz withdrawal. In one patient with pretreatment systolic pressure of 150 mm Hg, systolic pressure 48 h after drug withdrawal was 160 mm Hg. These studies, together with previous reports, suggest that guanabenz therapy for mild to moderate essential hypertension in doses of 32 mg/day or less can be safely withdrawn on an outpatient basis with a very low incidence of withdrawal phenomena.

Blood Pressure↗
PubMed1984

Renal alpha 1- and alpha 2-adrenoceptor mediated vasoconstriction in dogs: comparison of phenylephrine, clonidine, and guanabenz.

The alpha 2-agonist, guanabenz, increases Na and water excretion with little change in renal blood flow, while clonidine has been reported to cause antinatriuresis proportional to renal vasoconstriction. We hypothesized that clonidine-mediated renal vasoconstriction involves alpha 1-receptors. Dose-response curves were constructed correlating decreases in renal blood flow with doses of phenylephrine, clonidine, and guanabenz injected as boluses into renal arteries of anesthetized dogs. Changes in renal blood flow before and after prazosin, yohimbine or verapamil were recorded. Guanabenz was a 10-fold weaker vasoconstrictor than clonidine, but was still effective when alpha 1-receptors were blocked. Tenfold differences were found between phenylephrine, clonidine, and guanabenz for dependence on alpha 1-receptors. Denervation did not significantly shift the curves. Verapamil markedly attenuated only clonidine and guanabenz, which supported their dependence on calcium channels for vascular smooth muscle contraction. Thus, postsynaptic alpha 2-adrenoceptors can contribute to renal vasoconstriction in the dog but the receptors are either less numerous on the vasculature or are less efficiently coupled to contractile elements than are alpha 1-receptors. Clonidine constricts the renal vasculature through both adrenoceptor subtypes.

Animals↗
PubMed1984

Renal alpha 1- and alpha 2-adrenoceptor mediated vasoconstriction in dogs.

Clonidine (C) and guanabenz (G) are both alpha 2-agonists. Whereas C has been reported to cause anti-natriuresis proportional to renal vasoconstriction with acute infusion, G increases sodium and water excretion with little change in renal blood flow (RBF). C-mediated vasoconstriction may involve alpha 1-receptors. RBF in anaesthetized dogs was measured electromagnetically. Boluses of phenylephrine (P), C and G were injected into the renal artery via a perfusion cannula. Responses were expressed as delta RBF. Then prazosin or yohimbine were administered intra-arterially and dose-response curves repeated. The shift in dose ratio (delta ED50 after prazosin/yohimbine) for P was 52.9, for C was 4.7 and for G was 0.62. G was a 10-fold weaker vasoconstrictor than C, but G was still effective when alpha 1-receptors were blocked. Ten-fold differences were found between P, C and G for dependence upon alpha 1-adrenoceptors. Denervation did not significantly shift the curves. Thus, postsynaptic alpha 2-receptors can contribute to renal vasoconstriction, but the receptors are either less numerous or less efficiently coupled to contractile elements than in other beds. Verapamil markedly attenuated responses to C and G. Since tubular alpha 1-receptors have also been implicated in sodium transport, C may be more prone than G to cause anti-natriuresis both through stimulated tubular reabsorption and renal vasoconstriction.

Animals↗
PubMed1981

A vasoconstrictor cardiogenic chemoreflex induced by prostaglandin F2 alpha.

Systemic and skeletal muscle vascular responses to intracardiac prostaglandin F2 alpha (PGF2 alpha) were studied in anesthetized dogs. Resistance changes in a vascularly isolated but innervated reservoir-perfused gracilis muscle could occur only neurogenically. Injection of PGF2 alpha or serotonin (5-HT) raised systemic arterial blood pressure (BP) and caused reflex increases in gracilis muscle perfusion pressure (GMPP) that were abolished by alpha-adrenergic blockade. These changes in GMPP are opposite to the expected baroreceptor responses to an increase in BP. Subepicardial local anesthesia attenuated both delta BP and delta GMPP to 5-HT but only the delta GMPP to PGF2 alpha. Changes in BP and GMPP to 5-HT were reduced by vagotomy but not by stellate ganglionectomy. Conversely, stellate ganglionectomy significantly reduced the delta GMPP to PGF2 alpha but not the delta BP. Vagotomy affected neither delta BP nor delta GMPP following PGF2 alpha. Thus, while PGF2 alpha and 5-HT produce reflex vasoconstriction in gracilis muscle that is mediated through sympathetic efferent nerves and initiated by cardiogenic reflexes, apparently PGF2 alpha does so through sympathetic afferent and 5-HT through vagal afferent pathways. Further, since the systemic pressor response to PGF2 alpha persisted after stellatectomy, vagotomy, or local anesthesia, it is independent of the sympathetic cardiogenic chemoreflex.

Animals↗
PubMed1981

Acute and chronic effects of maternal ethanol administration on the ovine maternal-fetal unit.

The purpose of this study was to examine, in the pregnant ewe and its fetus, some of the physiological consequences of acute and chronic ethanol exposure. Ethanol was infused intravenously (2 g/kg/day over 2 h) to pregnant ewes from day 100 of pregnancy to term. Control animals received isocaloric infusions of 5% dextrose. Animals were pair-fed and allowed water ad lib. Maternal (n = 5) systolic, diastolic, and mean blood pressures and heart rate rose significantly by 1 h after starting ethanol, whereas fetal (n = 4) blood pressure and heart rate did not change during ethanol infusion. Maternal ethanol infusion produced a significant rise (p less than 0.01) in both fetal (n = 8) and maternal (n = 10) plasma cortisol levels. Peak blood ethanol concentration was significantly higher in the ewe (240 +/- 6 mg.dl-1, n = 7) than in the fetus (190 +/- 9 mg.dl-1, n = 6) at the end of the 2-hour infusion. Maternal rate of elimination after ethanol infusion was terminated was 40 mg.dl-1 per hour, while fetal elimination was 10 mg.dl-1 per hour. Body weights and crown-rump lengths of fetuses from 0.82 to 1.0 gestation were significantly less in ethanol-treated animals than in age-matched control animals. Fetal plasma thyroxine and triiodothyronine increments following thyrotrophin-releasing hormone administration were significantly less in alcohol-treated than in control animals. Thus, chronic exposure to ethanol during the latter part of gestation impaired fetal growth and altered fetal endocrine function in these animals.

Animals↗
PubMed1981

Mechanisms of the natriuretic and diuretic effects of prostaglandin F2 alpha.

The effects of prostaglandin F2 alpha on renal function were studied in hydropenic dogs. Peak responses occurred in 45 to 60 min. PGF 2 alpha (0.3 microgram.kg-1.min-1) increased urine flow by 1.3 +/- 0.3 ml/min and increased sodium excretion by 27.1 +/- 4.6 microEq/min. Papillary nonurea solute concentration was decreased from 981 +/- 153 to 347 +/- 58 mOsm/kg of H2O and the corticomedullary urea gradient was abolished. Although renal blood flow, glomerular filtration rate, peritubule capillary hydrostatic pressure and renal venous pressure were not changed by PGF2 alpha, urine from the infused kidney became distinctly hypotonic. A "washout" of medullary solutes was not supported by the data since the volume of distribution of 125I-albumin, an index of papillary perfusion rate, was not changed by PGF2 alpha. The contribution of decreased salt reabsorption from Henle's loop was evaluated in dogs that received furosemide and produced essentially isotonic urine. Subsequent intrarenal PGF2 alpha, increased CH2O and produced hypotonic urine with no significant further change in UNaV. These studies suggest that inhibition by PGF2 alpha of salt reabsorption from the thick ascending limb of Henle's loop may account for the modest natriuretic effect and contribute to the dissipation of the nonurea solute gradient. Additionally, there is an inhibition of both vasopressin-mediated water and urea reabsorption which contributed to the diuretic and hyposthenuric effects of infused prostaglandins.

Animals↗
PubMed1980

Inhibition of ADH-enhanced transepithelial urea and water movement by prostaglandins.

The effects of PGF2 alpha and PGE2 on transepithelial urea flux and osmotic water flow were evaluated in total bladders. Mucosal to serosal urea flux and osmotic water flow were not changed from basal values by the addition of either prostaglandin to the serosal bath. However, treatment with either PGF2 inhibited both urea flux and osmotic water flow in response to ADH stimulation in a concentration-dependent manner. The hydrosmotic response to ADH was more sensitive to prostaglandin inhibition than was urea flux. The inhibitory effect of the prostaglandins on ADH-enhanced urea flux was not dependent upon inhibition of the hydrosmotic response, since both PGF2 alpha and PGE2 decreased urea flux in the absence of a transepithelial osmotic gradient. Prostaglandin E2 was a more potent inhibitor than PGF2 alpha of both ADH-enhanced urea flux and osmotic water flow. The PGF2 alpha antagonism of osmotic water flow was apparently competitive, while antagonism of urea flux was apparently noncompetitive. The results are consistent with the hypothesis of the existence of a "spare" population of prostaglandin receptors that modulate water flow, but the absence of a "spare" prostaglandin receptor population with respect to the modulation of urea flux.

Animals↗
PubMed1979

Clearance and micropuncture studies of the diuretic xipamide in dogs.

Effects of the diuretic xipamide were examined by clearance and micropuncture techniques, and compared to clorothiazide. Xipamide decreased GFR and phosphate excretion. Reabsorption by superficial proximal tubules was unchanged. Since xipamide reduced single nephron filtration rate and GFR, a small effect on the proximal tubule may have been masked. Chlorothiazide decreased GFR but additionally decreased reabsorption by the proximal tubule. Xipamide was more chloruretic than natiuretic and probably inhibits reabsorption in the distal tubule.

Animals↗
PubMed1979

Antagonism of vasopressin-induced water flow by somatostatin.

The ability of somatostatin to modify the water premeability of the toad bladder was examined. Somatostatin had a small effect on basal water flow and antagonized the hydrosmotic effect of vasopressin. Water flow induced by cyclic AMP was enhanced. These results may explain the diuretic and hyposthenuric effects of somatostatin in vivo.

Animals↗
PubMed1978

The effects of prostaglandins E2 and F2alpha on synaptosomal accumulation and release of 3H-norepinephrine.

Prostaglandins (PG) of both the E and F series may serve as modulators of norepinephrine (NE) release from peripheral sympathetic neurons. We have studied the effects of PGE2 and PGF2alpha on the accumulation and release of 3H-NE in the CNS using synaptosomes isolated from rat hypothalami. The release of 3H-NE from synaptosomes superfused with Krebs-Ringer bicarbonate buffer was multiphasic with an initial fast release phase followed by a slower release. Raising KCl concentration of the superfusion medium to 56mM during the slow release phase is known to stimulate 3H-NE release. PGE2 (1 X 10(-6)M) attenuated 3H-NE release during the fast phase and reduced the amount of 3H-NE released due to KCl stimulation. At lower concentrations of PGE2 there was no change in the release profile. PGF2alpha was without effect on 3H-NE release at all concentrations tested. The accumulation of 3H-NE was significantly diminished by PGE2 at a concentration of 1 X 10(-6)M, while a lower concentration (1 X 10(-7)M) was ineffective. PGF2alpha had no effect on 3H-NE accumulation at all concentrations investigated.

Animals↗
PubMed1974

Proximal tubule reabsorption after hyperoncotic albumin infusion. Role of parathyroid hormone and dissociation from plasma volume.

Preferential expansion of the plasma volume by infusion of salt-poor hyperoncotic albumin solution decreases sodium reabsorption by the proximal tubule. The present micropuncture studies test the thesis that albumin infusion depresses proximal reabsorption by an effect unrelated to expansion of the plasma volume, perhaps due to an effect of parathyroid hormone (PTH) on proximal sodium reabsorption. Infusion of salt-poor hyperoncotic albumin significantly decreased plasma ionized calcium, increased immunoreactive PTH (iPTH) in plasma, decreased sodium reabsorption by the proximal tubule, and increased phosphate clearance. In contrast, infusions of albumin, in which the ionized calcium was restored to normal plasma levels, had no significant effect on ionized calcium, iPTH, proximal reabsorption, or phosphate clearance in intact dogs. Similarly, in parathyroidectomized animals given a constant replacement infusion of PTH, albumin infusion had no significant effect on proximal reabsorption or phosphate clearance. Plasma volume was markedly expanded following albumin infusion in all groups of dogs. These findings (a) indicate that PTH plays a significant role in the decrease in sodium reabsorption by the renal proximal tubule after salt-poor hyperoncotic albumin infusion, and (b) dissociate preferential expansion of the plasma volume from decreases in sodium reabsorption by the proximal tubule.

Absorption↗