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Biomedical subjects

H Holdaas

Publications and source records attributed to H Holdaas.

At least 73 records · Page 4Linked to original sources
PubMed1985

Modulation of reflex renal vasoconstriction by increased endogenous renal prostaglandin synthesis.

The effect of increased endogenous renal prostaglandin synthesis on the reflex renal vasoconstrictor response to stimulation of skeletal muscle somatic receptors and their afferents was examined in anesthetized dogs with bilateral carotid artery occlusion and vagotomy. Acute ureteral occlusion and indomethacin were used to acutely increase and decrease, respectively, endogenous renal prostaglandin synthesis. Graded electrical stimulation of the afferent sciatic nerve or antegrade femoral arterial injection of capsaicin elicited a frequency dependent reduction in renal blood flow accompanied by increases in mean arterial pressure and heart rate. Acute ureteral occlusion attenuated (circa 50%) the renal vasoconstrictor response but did not affect the increases in mean arterial pressure or heart rate. Administration of indomethacin during continued ureteral occlusion restored the renal vasoconstrictor responses to the preureteral occlusion level. These results indicate that the increase in endogenous renal prostaglandin synthesis during acute ureteral occlusion specifically attenuates the reflex renal vasoconstrictor response to stimulation of skeletal muscle somatic receptors and their afferents.

Animals↗
PubMed1984

Ouabain inhibits renin release by a direct renal haemodynamic effect.

The effect of intrarenal infusion of ouabain (90 micrograms/kg) on renin release was examined in the anaesthetized dog. Ouabain reduced cortical Na-K-ATPase activity to 23% and outer medullary activity to 18% of the control level. During renal arterial constriction to a perfusion pressure below the autoregulatory range, renin release rose from 1.2 +/- 0.4 to 47.4 +/- 6.9 micrograms/min (P less than 0.001). This response was abolished by ouabain. When superimposed on renal arterial constriction, beta-adrenergic stimulation enhanced renin release from 25.6 +/- 10.7 to 56.9 +/- 9.5 micrograms/min (P = 0.02) at a urinary sodium excretion of 2 +/- 1 mumol/min. After ouabain, the corresponding increment substantially decreased since release rose from 5.6 +/- 2.0 to 19.9 +/- 5.3 micrograms/min only (P = 0.02), at a urinary sodium excretion of 140 +/- 67 mumol/min. When glomerular filtration was reduced to zero by ureteral occlusion in one series, renin release increased to 22.6 +/- 5.1 but was reduced (P less than 0.05) by ouabain to 13.5 +/- 5.5 micrograms/min and superimposed isoproterenol had no effect. According to these observations, ouabain inhibits renin release by a direct effect on the afferent arteriole through constriction of the autoregulating renin-secreting segment.

Adrenergic beta-Agonists↗
PubMed1984

Evidence for bicarbonate-dependent lithium reabsorption in dog kidneys.

To examine whether lithium is reabsorbed along a transcellular or a paracellular route, experiments were performed in anesthetized volume-expanded dogs under conditions of constant glomerular filtration rate (GFR). Quabain, in doses inhibiting about 80% of Na, K-ATPase, and ethacrynic acid, another inhibitor of transcellular NaCl reabsorption, did not inhibit lithium or bicarbonate reabsorption. Lithium reabsorption increased in proportion to plasma concentration of lithium (PLi) up to 12 mM, suggesting a passive transport of lithium. During ouabain administration acetazolamide halved bicarbonate reabsorption, the main driving force for paracellular reabsorption, and halved the reabsorption of lithium. The reabsorbate concentration of lithium, calculated from data obtained before and after acetazolamide infusion, was almost equal to PLi. Mannitol, which reduces paracellular osmotic transport without affecting bicarbonate reabsorption, reduced lithium and chloride reabsorption in the same proportion as acetazolamide (r = 0.87). Combined acetazolamide and mannitol administration reduced fractional lithium reabsorption to 0.09 +/- 0.02. These data indicate that lithium is not actively transported but reabsorbed passively along a paracellular route by osmotic forces provided by transcellular NaHCO3 reabsorption.

Acetazolamide↗
PubMed1984

Relationship between PGE2 and renin release in dog kidneys. Effects of afferent arteriolar dilation and adrenergic stimulation.

To study the relationship between PGE2 and renin release from the kidney, examinations were performed on anesthetized dogs during afferent arteriolar dilation. This condition is known to increase renin release and enhance the stimulatory effects on renin release of beta-adrenergic agonists, such as isoproterenol. Afferent arteriolar dilation induced by constricting the renal artery or occluding the ureter increased PGE2 and renin release before, but not after, indomethacin administration. Isoproterenol infusion during afferent arteriolar dilation increased renin release but not PGE2 release both before and after indomethacin administration. Phenylephrine, an alpha-adrenergic agonist, which also induces afferent arteriolar dilation, increased PGE2 and renin release at control blood pressure but not when the afferent arterioles already were dilated by ureteral occlusion. We conclude that afferent arteriolar dilation caused by renal arterial constriction, ureteral occlusion or infusion of phenylephrine increases prostaglandin synthesis which stimulates renin release. The effect of isoproterenol on renin release is independent of prostaglandin synthesis.

Animals↗
PubMed1984

Glomerular filtration rate and PCO2 as determinants of lithium reabsorption.

To examine whether lithium reabsorption varies in proportion to the bicarbonate-dependent reabsorption of water and chloride, reabsorption was altered by varying PCO2 and glomerular filtration rate (GFR) in volume-expanded, anesthetized dogs during ethacrynic acid infusion. At constant GFR and plasma bicarbonate concentration, lithium, bicarbonate, chloride and water reabsorption were inversely related to plasma pH during variations in PCO2. Lithium and bicarbonate reabsorption varied by 9 +/- 1% and chloride reabsorption by 7 +/- 1% as plasma pH was altered by 0.1 unit from plasma pH 7.5. Calculation of reabsorbate concentrations indicated that lithium was reabsorbed as readily as water (reflection coefficient = 0). During mechanical constriction of the suprarenal aorta, GFR was reduced at constant plasma pH. Bicarbonate reabsorption fell more than chloride, water and lithium reabsorption. Lithium reabsorption was not significantly reduced until GFR was reduced by 35%. In stop-flow studies during ouabain infusion, urinary lithium concentrations were reduced below plasma concentrations. This is compatible with passive diffusion of lithium along a lumen-positive potential exceeding 10 mV in the diluting segment. Thus, lithium reabsorption behaved as expected for bicarbonate-dependent paracellular reabsorption during variations in PCO2; when GFR is reduced, an additional component of lithium reabsorption is disclosed.

Absorption↗
PubMed1984

Site and magnitude of the tubular inhibitory effect of expanding the extracellular volume in dogs.

Ethacrynic acid inhibits energy-requiring transcellular NaCl reabsorption without affecting NaHCO3 reabsorption. Acetazolamide inhibits NaHCO3 and most of the remaining NaCl reabsorption in the proximal tubules (bicarbonate-dependent reabsorption) but raises distal transcellular NaCl reabsorption. After administration of both diuretics, the remaining bicarbonate-dependent and transcellular reabsorptions become constant until glomerular filtration rate (GFR) is almost halved. The inhibitory effect of expanding the extracellular volume (ECV) until plasma volume and GFR increased 30-40% was examined in anesthetized dogs. Examinations at comparable GFR obtained by altering arterial perfusion pressure showed that the inhibitory effect of ECV expansion was attenuated by administering acetazolamide. Ethacrynic acid amplified the inhibitory effect which for sodium and chloride reabsorption amounted to 6-7% of the filtered load at comparable GFR. An inhibitory effect of ECV expansion of bicarbonate reabsorption was disclosed only after raising plasma bicarbonate concentration. Thus, the small inhibitory effect of massive ECV expansion is confined to proximal tubular bicarbonate-dependent reabsorption and is of the same magnitude as previously demonstrated in experiments of similar design by raising plasma pH by only 0.07 unit. Since ouabain inhibits transcellular NaCl reabsorption, a natriuretic hormone is more likely to be an inhibitor of carbonic anhydrase than of Na,K-ATPase.

Absorption↗
PubMed1984

Stimulatory and inhibitory reflexes from somatic receptors: effect on renin release.

The effect of stimulation of skeletal muscle somatic receptor afferents on renal function and renin release was examined in anesthetized dogs (bilateral carotid occlusion and vagotomy) with controlled renal arterial pressure. Afferent sciatic nerve stimulation (20-40 V, 1 ms) at 0.6-1.5 Hz elicited cardiovascular pressor responses, renal vasoconstriction, and stimulation of renin release, whereas at 0.3-0.8 Hz cardiovascular depressor responses and inhibition of renin release without changes in renal blood flow were found. Renal denervation abolished the inhibition of renin release but not the cardiovascular depressor response to afferent sciatic nerve stimulation at 20-40 V, 1 ms, and 0.3-0.8 Hz. Peripheral somatic afferent nerves contain fibers which, when appropriately stimulated, produce either pressor or depressor cardiovascular responses. At constant renal arterial pressure, increases in renin release occur with pressor responses, whereas decreases in renin release, mediated by the renal nerves, occur with depressor responses.

Afferent Pathways↗
PubMed1984

On the existence of renal vasodilator nerves.

The renal vasoconstrictor responses to graded frequencies of direct electrical renal nerve stimulation and renal arterial norepinephrine injections were evaluated before and during renal alpha-1 adrenoceptor blockade in anesthetized dogs. Renal alpha-1 adrenoceptor blockade was achieved by infusing increasing doses (1, 10, 20, 40 micrograms/kg/min) of prazosin, a selective postsynaptic alpha-1 adrenoceptor antagonist, into the renal artery. The renal vasoconstrictor response to norepinephrine (1.5 micrograms) was completely abolished by 10 micrograms/kg/min prazosin. However, the renal vasoconstrictor response to a frequency of renal nerve stimulation which produced less renal vasoconstriction than norepinephrine (1.5 micrograms) in the absence of prazosin was not abolished by either 10, 20, or 40 micrograms/kg/min prazosin. During prazosin administration, neither renal nerve stimulation nor norepinephrine produced renal vasodilatation. Therefore, at prazosin doses two- and fourfold greater than that demonstrated to produce complete renal alpha-1 adrenoceptor blockade, no renal vasodilator responses to graded renal nerve stimulation were observed. These studies provide no evidence in support of a neural renal vasodilator mechanism in the dog.

Animals↗
PubMed1983

Segmental distribution of vascular resistances during ureteral occlusion. The vasoconstrictive effects of angiotensin and CaCl2 differ from those of catecholamines and renal nerve stimulation.

UNLABELLED: Examinations of renal autoregulation and renin release suggest that alpha-adrenergic agonists, in contrast to other vasoconstrictors, preferentially constrict the preglomerular arteries. To examine this hypothesis, experiments were performed in anesthetized dogs during ureteral occlusion. At a ureteral pressure (UP) of 100 mmHg the afferent arterioles are dilated and mechanical constriction of the renal artery does not alter intrarenal vascular resistances. Whereas angiotensin and CaCl2 infused into the renal artery reduced renal blood flow (RBF) by 25-30% without reducing UP, renal nerve stimulation reduced RBF and UP in proportion. During angiotensin and catecholamine infusion, measurements of UP and intrarenal venous pressure permitted calculations of preglomerular, efferent vascular and intrarenal venous resistances. Until RBF was reduced by 25%, angiotensin raised both preglomerular and efferent vascular resistances, whereas norepinephrine and the alpha-adrenergic agonists, phenylephrine and methoxamine, raised preglomerular more than efferent vascular resistance. When RBF was reduced by more than 25%, all vasoconstrictors showed a similar pattern with large increments both in preglomerular and efferent vascular resistances. CONCLUSIONS: Humoral and nervous stimulation of alpha-adrenergic receptors reduce glomerular capillary pressure by preferentially constricting the preglomerular arteries and may affect renal autoregulation and renin release by reducing the transmural pressure of the afferent arterioles.

Adrenergic alpha-Agonists↗
PubMed1983

Conditions for augmentation of renin release by theophylline.

Isoproterenol, dopamine, glucagon and dibutyryl cyclic AMP (DB-cAMP) increase renin release at low but not at control blood pressure. These findings suggest that autoregulated afferent arteriolar dilation is a prerequisite of renin release mediated by intracellular generation of cyclic AMP. To examine this hypothesis further the effects on renin release of theophylline, which would maintain high intracellular concentration of cAMP by inhibiting phosphodiesterase, were studied in anesthetized dogs. After inhibiting beta-adrenergic stimulation with propranolol, theophylline increased renin release significantly from 0.7 +/- 0.2 to 1.8 +/- 0.7 micrograms/min at control blood pressure and from 23 +/- 4 to 41 +/- 5 micrograms/min at a renal perfusion pressure of about 50 mmHg. The greater effect at low blood pressure occurred despite adjustment of the infusion rate of theophylline to keep arterial plasma concentration of theophylline unaltered. Isoproterenol infusion at low blood pressure raised renin release from 41 +/- 11 to 76 +/- 19 micrograms/min before and 54 +/- 13 to 108 +/- 31 micrograms/min during continuous infusion of theophylline. The renin release response to infusion of theophylline at low blood pressure was not enhanced by DB-cAMP infusion. We conclude that arteriolar dilation provides a condition for stimulation of renin release during the theophylline infusion. Theophylline infusion may augment the effect of isoproterenol on renin release by delaying the intracellular degradation of cAMP.

Animals↗
PubMed1982

Conditions for enhancement of renin release by isoproterenol, dopamine, and glucagon.

Isoproterenol infusion increases renin release at low but not at control blood pressure. To examine whether this effect is dependent on arteriolar dilation and is specific for agonists of beta-adrenoceptors, responses to intrarenal infusion of isoproterenol (0.2 micrograms.kg body wt-1.min-1), glucagon (0.1 micrograms.kg body wt-1.min-1), and dopamine (1 micrograms.kg body wt-1.min-1) were compared at control and low or high ureteral pressure, which also dilates the renal arterioles. During renal arterial constriction, renin release was equal at two perfusion pressures below the range of autoregulation and was 76 +/- 24 micrograms/min higher during isoproterenol than during propranolol administration. Intravenous infusion of isoproterenol gave qualitatively similar results. Intrarenal infusion of glucagon and dopamine increased renin release by 13 +/- 3 and 22 +/- 12 micrograms/min, respectively; enhancement of renin release was also present after propranolol administration. During ureteral occlusion, intrarenal infusion of isoproterenol, dopamine, and glucagon increased renin release from 30-40 micrograms/min by 78 +/- 11, 13 +/- 3, and 31 +/- 10 micrograms/min, respectively. At control blood and ureteral pressure, the effects on renin release of infusing isoproterenol, dopamine, or glucagon were small or absent. Thus, isoproterenol, dopamine, amd glucagon enhance renin release when the arterioles are dilated by renal arterial constriction or ureteral occlusion.

Animals↗
PubMed1981

Filtered bicarbonate and plasma pH as determinants of renal bicarbonate reabsorption.

To examine if bicarbonate reabsorption varies with filtered bicarbonate and plasma pH, we infused anesthetized dogs i.v. with sodium chloride and sodium bicarbonate to alter plasma bicarbonate concentration (PHCO3) without changing hematocrit. Examinations in five dogs over a wide range of glomerular filtration rates (GFR) during ethacrynic acid infusion showed that bicarbonate reabsorption at equal filtered load and equal plasma pH of 7.5 was not significantly changed by increasing PHCO3 from 30.2 +/- 0.4 to 55.2 +/- 0.6 mM and PCO2 from 33.8 +/- 0.7 to 74.1 +/- 2.1 mm Hg. Examinations during respiratory and metabolic alkalosis in five dogs at plasma pH of 7.8 showed that bicarbonate reabsorption at equal filtered load was not significantly different at a PCO2 of 20.2 +/- 0.8 and 36.8 +/- 0.8 mm Hg. Finally, in five dogs that did not receive ethacrynic acid, plasma pH was lowered by inducing respiratory acidosis at a PHCO3 of 30 mM and raised during progressive respiratory and metabolic alkalosis, Bicarbonate reabsorption was linearly related to plasma pH within the range 7.1 to 7.85 (r = 0.92). By altering plasma pH by 0.1 unit, bicarbonate reabsorption was altered by 10 +/- 1%. Thus, filtered bicarbonate rather than GFR and plasma pH rather than PCO2 are important acute regulators of bicarbonate reabsorption. This regulation may be achieved by determining pH and bicarbonate concentration in the luminal fluid along the proximal tubules.

Alkalosis↗
PubMed1981

Effect of low-level renal nerve stimulation on renin release from nonfiltering kidneys.

The mechanism whereby renal nerves influence the renin-release response to aortic constriction was examined in a nonfiltering ureter-occluded kidney preparation in anesthetized dogs. The kidney was rendered nonfiltering by a combination of mannitol infusion and ureteral occlusion. Suprarenal aortic constriction reduced renal perfusion pressure to 61 +/- 7 mmHg and increased renin release from 16.7 +/- 4.1 to 26.1 +/- 6.0 U/min. At normal renal perfusion pressure, low-frequency renal nerve stimulation (0.25 Hz) increased renin release by 11.6 +/- 4.2 to 25.1 +/- 7.6 U/min. The effect of combined low-level renal nerve stimulation and aortic constriction on renin release was additive; renin release increased by 24.6 +/- 6.5 to 39.5 +/- 7.3 U/min. Propranolol or metoprolol, administered intrarenally at 2 microgram . min-1 . kg-1, abolished the renin-release response to low-level renal nerve stimulation at normal renal perfusion pressure. These data provide evidence that low-frequency renal nerve stimulation influences the renin-release response to reduction in renal perfusion pressure in a nonfiltering ureter-occluded kidney with an inoperative macula densa receptor mechanism. The neural effect on renin release at normal renal perfusion pressure is mediated via beta 1-adrenoceptors probably located on the juxtaglomerular granular cells.

Animals↗
PubMed1981

Conditions for humoral alpha-adrenoceptor stimulation of renin release in anaesthetized dogs.

To examine whether an alpha-adrenergic agonist, methoxamine, influences renin release solely by its haemodynamic effect, experiments were performed in anaesthetized dogs with denervated kidneys. Methoxamine was infused intrarenally at rates which reduced renal blood flow (RBF) by 30-40%. At control blood pressure, renin release rose during infusion of methoxamine from 1.4 +/- 0.7 to 31 +/- 11 microgram/min. A beta-adrenergic stimulator, isoproterenol, did not increase renin release significantly when administered alone into the renal artery, but doubled the effect of methoxamine infusion: at control blood pressure renin release rose from 0.5 +/- 0.3 to 71 +/- 17 microgram/min during combined infusion of isoproterenol and methoxamine. Mechanical constriction of the renal artery left RBF unaltered down to a renal perfusion pressure of 90 +/- 4 mmHg during methoxamine infusion, whereas the lowest autoregulating pressure in control experiments averaged 60 +/- 5 mmHg. At renal infusion pressure below the range of autoregulation, renin release was not further increased by intrarenal infusion of methoxamine. Isoproterenol infusion at low renal perfusion pressure doubled renin release, which was not significantly altered by additional infusion of methoxamine. The stimulatory effect of methoxamine on renin release at control blood pressure could be diminished but not prevented by infusing 2.9% NaCl intravenously in large amounts. These data indicate that methoxamine induces autoregulated dilation of afferent arterioles by disproportionate vasoconstriction on pre-afferent arteries. Thereby afferent arterioles are conditioned for stimulation of renin release by isoproterenol.

Animals↗
PubMed1981

Conditions for stimulation of renin release by cyclic AMP in anaesthetized dogs.

Cyclic AMP (cAMP) is the intracellular mediator of beta-adrenergic stimulation in most tissues. Stimulation of beta-adrenoceptors increases renin release much more at low than at control arterial perfusion pressure. If beta-adrenergic stimulation is mediated by cAMP, this nucleotide should also potentiate renin release at low perfusion pressure. In anaesthetized, propranolol treated dogs, the dibutyryl derivative of cAMP (DB-cAMP), which penetrates cell membranes more readily than cAMP, increased renin release significantly during renal arterial constriction at a perfusion pressure below the range of autoregulation, but no significant effect was observed at control blood pressure. A dose-response relationship could be demonstrated in propranolol treated dogs by administering DB-cAMP at 10, 100 and 1000 micrograms/min at low but not at control blood pressure. Since sodium excretion increased, stimulation of a macula densa mechanism is unlikely, whereas arteriolar dilation, caused by autoregulation at low blood pressure, may condition the juxtaglomerular apparatus for renin release. Infusion of cAMP had no effect on renin release either at control or low blood pressure, whereas 5'AMP exerted a marked inhibitory effect at low blood pressure. We conclude that infusion of DB-cAMP rather than cAMP stimulates renin release at low but not at control blood pressure and that this effect is not mediated by beta-adrenergic receptors; cAMP may be an intracellular mediator of renin release.

Adenosine Monophosphate↗
PubMed1981

Mechanism of renin release during renal nerve stimulation in dogs.

During renal nerve stimulation, a predominant vasoconstrictory effect on small arteries would lower blood pressure in the afferent arterioles and induce arteriolar dilation and renin release by the autoregulation mechanism. This hypothesis was examined in anaesthetized dogs by stimulating renal nerves at 4 Hz which permitted continuous reduction of renal blood flow (RBF) by 30-40%; renin release increased almost equally at control and low blood pressure, and in the non-filtering kidney during ureteral occlusion. Examinations of the relationship between RBF and arterial perfusion pressure during mechanical constriction of the renal artery showed that the lowest autoregulating pressure was 25-35 mmHg higher during nerve stimulation than in control experiments, consistent with the hypothesis of arteriolar dilation. Phenoxybenzamine, an inhibitor of alpha-adrenoceptors, abolished vasoconstriction and the effect of nerve stimulation on renin release at control blood pressure; renin release rose from 0.9 +/- 0.4 to 17 +/- 5 microgram/min before, and from 1.7 +/- 0.5 to 4.6 +/- 1.4 microgram/min after phenoxybenzamine infusion. At pressures below the range of autoregulation, phenoxybenzamine did not alter renin release response to nerve stimulation. Propranolol, a Beta-adrenergic inhibitor, attenuated the effect of nerve stimulation on renin release both at control and low blood pressure. We conclude that during renal nerve stimulation (1) renin release is caused by beta-adrenergic stimulation provided the afferent arterioles are dilated and (2) that alpha-adrenergic stimulation dilated the afferent arterioles as a consequence of a predominant vasoconstrictory effect on small arteries. Hence, by inhibiting the beta-adrenergic effect by propranolol, renin release does not increase during renal nerve stimulation. Phenoxybenzamine prevents renin release at control blood pressure because afferent arterioles are not dilated during nerve stimulation. In contrast, phenoxybenzamine does not reduce renin release during nerve stimulation at low blood pressure because afferent arterioles are dilated by the autoregulating mechanism.

Animals↗