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Biomedical subjects

J L Izzo

Publications and source records attributed to J L Izzo.

At least 55 records · Page 3Linked to original sources
PubMed1989

Adrenergic control of renin during dietary sodium deprivation in conscious dogs.

These experiments evaluated the contribution of alpha- and beta-adrenergic stimulation to plasma renin activity (PRA) during early and long-term dietary sodium restriction, compared with normal sodium intake. Uninephrectomized conscious dogs with catheters in the aorta, vena cava, and remaining renal artery were studied during normal sodium diet (approximately 70 meq/day), after 2-3 days of low-sodium diet (5-7 meq/day), and after greater than or equal to 2 wk of low-sodium diet. Direct renal arterial (ira) infusion of phenoxybenzamine plus propranolol decreased PRA by similar proportions (39-48%) during all three states of dietary sodium intake. The PRA achieved after adrenergic blockade remained higher (P less than 0.05) during early and long-term sodium restriction than during normal sodium intake. The effect on PRA of ira infusion of propranolol alone was not different from that of phenoxybenzamine plus propranolol during normal or low-sodium diet, and the magnitude of decrease in PRA during low-sodium diet was the same whether propranolol (1 microgram.kg-1.min-1) was infused ira or intravenously. In summary, beta-adrenergic stimulation accounts for similar proportions of PRA during early and long-term dietary sodium restriction and during normal sodium intake. Renal alpha-adrenoceptors appear to play little or no role in control of PRA under these conditions.

Animals↗
PubMed1988

Adrenergic control of renin in euhydrated and water-deprived conscious dogs.

These experiments evaluated the relative contributions of alpha- and beta-adrenoceptors to control of plasma renin activity (PRA) in conscious dogs in which PRA was elevated to two- and threefold basal levels by the orthostatic stress of passive quadruped standing and by 24-h water deprivation. All dogs were uninephrectomized and surgically prepared with chronically indwelling catheters in the aorta, vena cava, and remaining renal artery at least 10 days before experiments. Simultaneous direct renal arterial (ia) infusion of phenoxybenzamine and propranolol decreased PRA by 50% in euhydrated standing dogs and by 70% in dehydrated standing dogs without changing mean arterial pressure or heart rate. In euhydrated dogs, both ia phenoxybenzamine alone and ia propranolol alone significantly decreased PRA, but the effect of propranolol was greater than that of phenoxybenzamine. In dehydrated dogs, ia infusion of phenoxybenzamine alone did not significantly decrease PRA, whereas propranolol alone decreased PRA to nearly the same extent as combined ia alpha- and beta-adrenoceptor blockade. The majority of the adrenergically mediated component of PRA observed during orthostatic stress and dehydration in conscious dogs is therefore mediated by beta-adrenoceptors. However, PRA was similarly reduced whether propranolol was infused ia or intravenously. Thus the site of action of propranolol (intrarenal vs. extrarenal) could not be identified by these experiments.

Aldosterone↗
PubMed1987

Chronic effects of direct vasodilation (pinacidil), alpha-adrenergic blockade (prazosin) and angiotensin-converting enzyme inhibition (captopril) in systemic hypertension.

Chronic responses of systemic hemodynamics and blood pressure counterregulatory ("pseudo-tolerance") mechanisms were investigated in matched groups of patients with essential hypertension after 1 month of vasodilator therapy with pinacidil (a direct arterial dilator), prazosin (an alpha 1-adrenergic blocking drug) or captopril (an angiotensin-converting enzyme inhibitor). For equivalent decreases in mean arterial pressure compared with placebo baseline (approximately 8 mm Hg supine and 12 mm Hg upright), prazosin and captopril did not increase cardiac index or heart rate. In contrast, marked decreases in systemic vascular resistance with pinacidil (approximately 25%, p less than 0.05) were accompanied by reflex increases in cardiac index (approximately 20%, p less than 0.05). Activity of the sympathetic nervous system, measured by supine and upright plasma norepinephrine (NE), increased approximately 50% with pinacidil and prazosin (p less than 0.001 each), whereas captopril decreased supine plasma NE by 12% (p less than 0.05) and did not change upright plasma NE. All 3 drugs caused an expansion of height-adjusted blood volume (approximately 14%). Pinacidil and prazosin caused reversible weight gains of 0.9 and 0.7 kg, respectively, whereas captopril reversibly decreased body weight by 0.8 kg (p less than 0.05), suggesting differential effects of the 3 drugs on interstitial fluid volume. During chronic therapy, all 3 drugs may require concomitant diuretic therapy, whereas concomitant sympatholytic therapy may be required with the potent vasodilator pinacidil. Captopril may be associated with the lowest cardiac risk because of its lack of stimulatory effects on the sympathetic nervous system and cardiac index.

Adrenergic alpha-Antagonists↗
PubMed1987

Adrenal medullary regulation of rat renal cortical adrenergic receptors.

The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particulate fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of [3H]prazosin, [3H]rauwolscine, and [125I]iodocyanopindolol were used to quantitate alpha 1-, alpha 2-, and beta-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (Bmax, per milligram membrane protein) for alpha 1-, and alpha 2-, and beta-adrenergic receptors were increased by 22, 18.5, and 25%, respectively (P less than 0.05 for each). No differences were found in the equilibrium dissociation constants (KD) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation (P less than 0.01); renal cortical epinephrine was not detectable in control or demedullated animals. Our results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine.

Adrenal Medulla↗
PubMed1987

Plasma norepinephrine and age as determinants of systemic hemodynamics in men with established essential hypertension.

Two primary predictor variables, age and supine plasma norepinephrine, were studied with respect to their influences on supine hemodynamic variables in 52 white men with essential hypertension who were 23 to 67 years of age and had been off active therapy for at least 4 weeks. Plasma norepinephrine was related to age (r = 0.39, p less than 0.01), correlated closely with mean arterial pressure (MAP; r = 0.54, p less than 0.0002) and systemic vascular resistance (r = 0.49, p less than 0.0005), and was related inversely to cardiac output (r = -0.26, p less than 0.06) and stroke volume (r = -0.31, p less than 0.05). Age correlated weakly with MAP (r = 0.31, p less than 0.05) and more strongly with systemic vascular resistance (r = 0.46, p less than 0.005) but was negatively related to cardiac output (r = -0.41, p less than 0.005) and heart rate (r = -0.33, p less than 0.05). Weight did not correlate with any of the hemodynamic variables. Partial regression techniques yielded significant residual correlations between age-adjusted plasma norepinephrine and MAP (r = 0.42, p less than 0.005) or systemic vascular resistance (r = 0.38, p less than 0.005). Residual correlations with cardiac output (r = -0.34, p less than 0.05), heart rate (r = -0.36, p less than 0.02), and systemic vascular resistance (r = 0.33, p less than 0.05) remained after adjusting age for the corresponding plasma norepinephrine values. These correlations demonstrate the independent effects of sympathetic nervous activity and the aging process on the systemic vasoconstriction and decreased cardiac function observed in essential hypertension.

Adult↗
PubMed1987

Increased plasma norepinephrine and sympathetic nervous activity in essential hypertensive and uremic humans: effects of clonidine.

We investigated the relationship between hypertension and increased sympathoadrenal activity in previously normotensive, stable maintenance hemodialysis patients (uremics) who developed hypertension subsequent to the onset of chronic renal failure. In age-matched groups, supine morning plasma norepinephrine (NE) concentrations (pg/ml) were elevated in uremics (401 +/- 26, p less than 0.00001, n = 23) and essential hypertensives (340 +/- 23, p less than 0.01, n = 29) compared to normal controls (260 +/- 18, n = 24). To further investigate the functional significance of increased sympathoadrenal activity in uremia, a subset of dialysis patients was studied during chronic clonidine therapy. Compared to placebo baseline, clonidine (mean dose 0.4 mg/day) caused parallel decreases in mean arterial pressure (MAP) (-8 +/- 2 mm Hg, p less than 0.05), heart rate (HR) (-13 +/- 3 b/min, p less than 0.05), plasma NE (-84 +/- 13 pg/ml, p less than 0.01), and plasma epinephrine (-24 +/- 4 pg/ml, p less than 0.01). Clonidine exerted balanced effects on cardiac output and systemic vascular resistance while blood volume and plasma renin activity were slightly increased. We conclude that the increased sympathoadrenal activity in uremia contributes to chronically increased arterial pressure in a pattern similar to essential hypertension. Central sympatholytic drugs are effective antihypertensive agents in uremia.

Adult↗
PubMed1987

Captopril reduces urinary cystine excretion in cystinuria.

Cystinuria is characterized by cystine stone formation and loss of renal function. Conservative therapy is generally ineffective and penicillamine therapy can be complicated by serious side effects. To our knowledge, we report the first clinical use of captopril in the treatment of homozygous cystinuria in two siblings. In the first patient, a 70% reduction in cystine excretion was observed after 26 weeks of therapy with 150 mg/d of captopril. Discontinuation of use of the drug resulted in a return to baseline cystine excretion, further loss of renal function, and nephrotic range proteinuria. Repeated treatment with captopril stabilized renal function, reduced proteinuria, and returned cystine excretion to near normal levels. In the second patient, cystine excretion was reduced by 93% after nine weeks of therapy with 75 mg/d of captopril. No adverse side effects were observed in either patient. Formation of the captopril-cysteine disulfide accounts for part of the reduction in cystine excretion but other mechanisms probably contribute. Because captopril-cysteine disulfide is 200 times more soluble than cystine, long-term captopril therapy may be useful in the treatment of cystinuria.

Adult↗
PubMed1986

The role of the sympathetic nervous system in 2-kidney DOCA-hypertensive Yucatan miniature swine.

To assess the mechanism responsible for maintaining the elevated arterial pressure in 2-kidney DOCA treated Yucatan miniature swine, cardiovascular parameters and the responses to hexamethonium bromide (HMB) were evaluated in normal and DOCA treated animals. Using chronically instrumented conscious animals, measurements of mean arterial pressure (MAP), cardiac output (CO), and calculated total peripheral resistance (TPR) revealed that with DOCA hypertension MAP was increased 50-60 mmHg above controls. This increased pressure was due to an increase in TPR with CO remaining normal. HMB normalized the MAP of the DOCA animals via a selective lowering of TPR to a value similar to that of the controls. In DOCA hypertensive animals these functional changes, due to increased peripheral sympathetic nerve activity, were reflected by significantly elevated plasma norepinephrine. In this animal DOCA administration produces a neurogenic form of hypertension which appears to be analogous to essential hypertension in man.

Animals↗
PubMed1985

Plasma dihydroxyphenylglycol (DHPG) in the in vivo assessment of human neuronal norepinephrine metabolism.

We investigated the utility of deaminated norepinephrine (NE) metabolites in the study of human sympathetic nervous pathophysiology. Plasma levels of the NE metabolite dihydroxyphenylglycol (DHPG) appear to be related to intraneuronal NE stores. Plasma DHPG increases when sympathetic nervous activity or circulating NE increase and decreases when neuronal NE is depleted or neuronal NE reuptake is blocked. Changes in plasma dihydroxymandelic acid (DOMA) related less closely to changes in plasma NE. The coupling of measurements of plasma NE with its deaminated metabolites and DHPG may improve understanding of human NE metabolism and neuronal NE reuptake.

Glycols↗
PubMed1985

Influence of renal perfusion pressure on alpha- and beta-adrenergic stimulation of renin release.

Experiments were performed in pentobarbital-anesthetized dogs to 1) determine if neural stimulation of renin release can be mediated by renal alpha-adrenoceptors at renal nerve stimulation (RNS) frequencies that have little or no effect on total renal blood flow (less than or equal to 1.2 Hz) and 2) ascertain whether alpha-adrenergic control of renin release is affected by renal perfusion pressure (RPP). The renal nerves were electrically stimulated both in the absence of RPP control and with RPP controlled near 85 mmHg. Decreased RPP lowered the threshold for neurogenic stimulation of renin release from less than or equal to 1.2 to 0.3 Hz. beta-Adrenoceptor blockade with propranolol blunted the renin secretion rate (RSR) response to graded RNS (0.3-5.0 Hz), but the extent of inhibition during low-frequency RNS was dependent on RPP. Propranolol prevented increased RSR at 0.6-1.2 Hz RNS when RPP was 111-120 mmHg but not when RPP was 85 mmHg. Combined alpha- and beta-blockade with prazosin and propranolol totally prevented increased RSR during 0.6-1.2 Hz RNS at reduced RPP. In summary, both alpha- and beta-adrenoceptors mediate neural stimulation of renin release at RNS frequencies that do not decrease total renal blood flow when RPP is 85 mmHg.

Animals↗
PubMed1984

Renal norepinephrine overflow during graded renal nerve stimulation before and after beta-adrenoceptor blockade.

These experiments were designed to determine if renal venous norepinephrine (NE) overflow provides a valid index of renal sympathetic nerve activity. In addition, we evaluated the effect of beta-adrenoceptor blockade on renal NE overflow during graded renal nerve stimulation in order to examine the possibility that presynaptic beta-adrenoceptors facilitate neuronal release of NE in the kidney. In 6 pentobarbital-anesthetized dogs, the renal nerves were transected to remove tonic nerve activity and the distal ends were electrically stimulated (8-25 V, 0.5 ms) over the range of 0.3-5.0 Hz for consecutive 4-min periods. NE overflow rate was calculated as the product of the veno-arterial NE concentration difference and renal plasma flow. Control values of NE overflow (-8.7 +/- 1.8 ng/min) demonstrated net clearance of NE from the renal circulation. NE overflow rate rose to -3.1 +/- 2.2, 1.0 +/- 4.0, and 33.2 +/- 15.4 ng/min at 0.3, 0.6, and 1.2 Hz stimulation, respectively, with no accompanying change in renal blood flow. At 2.4 and 5.0 Hz, renal blood flow decreased by 21 +/- 4% and 37 +/- 3%, but there was no further increase in NE overflow rate (38.8 +/- 9.4 and 27.8 +/- 6.5 ng/min). Propranolol (0.5-1.0 mg . kg-1 plus 0.4-0.5 mg . kg-1 i.v., n = 4) did not alter the effect of nerve stimulation on either NE overflow or renal blood flow. Thus we were unable to demonstrate the presence of functional renal presynaptic beta-adrenoceptors. Further, our data indicate that renal norepinephrine overflow rate is not always a reliable index of renal nerve activity, since NE overflow was not proportional to renal nerve stimulation rate at frequencies high enough to cause vasoconstriction.

Animals↗
PubMed1984

Hemodynamic response to volume depletion in acutely uremic dogs.

Hemodynamic response to volume depletion by isolated ultrafiltration was compared in uremic (U) and nonuremic (N) conscious dogs. Fluid was removed at a constant rate until mean arterial pressure (MAP) decreased to less than 80 mmHg. Initial MAP was higher in the uremic dogs [132 +/- 8.6 (SD) mmHg] than in nonuremic controls (106 +/- 12, P less than 0.001). Initial cardiac index [U 4.97 +/- 0.831 X min-1 X m-2, N 4.44 +/- 0.62] and total peripheral vascular resistance index [(TPRI) U 2,160 +/- 353 dyn X s X cm-5 X m-2, N 1,976 +/- 420] were slightly, but not significantly, higher in uremic animals. Initial central venous pressure, wedge pressure, and plasma norepinephrine level were greater in the uremic dogs. At the end point of volume depletion, both uremic and nonuremic animals had achieved similar levels of TPRI, despite greatly attenuated or absent increases in plasma renin activity in the uremic group. At end point, blood volumes and plasma norepinephrine levels were comparable. The increase in pulse rate was higher in the uremic animals (59 +/- 37 pulses/min) compared with controls (25 +/- 52, P less than 0.05). In an additional group of uremic dogs, cardiovascular responses to hemorrhage and isolated ultrafiltration were compared and found to be similar, after allowance for blood viscosity changes had been made. The data suggest that in acutely uremic conscious dogs, despite reduced renin-angiotensin responses, hemodynamic adaptation to rapid volume depletion is not impaired.

Animals↗
PubMed1983

Age and prior caffeine use alter the cardiovascular and adrenomedullary responses to oral caffeine.

The effects of age and chronic caffeine use (approximately 300 mg/day) on the cardiovascular and humoral responses to 250 mg of oral caffeine (the equivalent of 2 to 3 cups of coffee) were examined. Older subjects had greater increases in blood pressure than younger subjects (p less than 0.03), and caffeine nonusers had greater blood pressure increases than caffeine users, regardless of age (p less than 0.05). Caffeine increased the product of systolic blood pressure and heart rate (an estimate of myocardial oxygen demand) in older caffeine nonusers, but this effect was absent in older caffeine users (p less than 0.01). Cardiovascular effects of caffeine could not be related temporally to changes in plasma epinephrine, which were greater in caffeine nonusers and younger subjects, or to plasma norepinephrine, renin activity or vasopressin, which did not change. Thus, age accentuates and moderate prior caffeine use attenuates the cardiovascular effects of oral caffeine; these effects are not mediated solely through the sympathoadrenal system.

Adrenal Medulla↗
PubMed1983

Radioenzymatic assay for plasma dihydroxyphenylglycol (DHPG), dihydroxymandelic acid (DOMA) and dihydroxyphenylacetic acid (DOPAC).

An adaptation of the single-isotope radioenzymatic catecholamine assay technique allows simultaneous quantitation of free dihydroxyphenylglycol (DHPG), dihydroxymandelic acid (DOMA), and dihydroxyphenylacetic acid (DOPAC) in small volumes of plasma. Incubation of sample with catechol-O-methyltransferase and S-adenosylmethionine is followed by acidic extractions of metabolites and thin-layer chromatography. O-methylated products of the beta-hydroxylated metabolites DHPG and DOMA are further subjected to periodate cleavage to improve sensitivity. Quantitation by liquid scintillation counting with internal standardization results in a sensitivity of approximately 8, 30 and 70 pg for DHPG, DOMA and DOPAC. Normal values for these three metabolites in resting humans are (mean +/- S.D., pg/ml): 1010 +/- 280 for DHPG, 2090 +/- 720 for DOMA and 3270 +/- 1470 for DOPAC.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Fludrocortisone suppression of sympathetic nervous activity.

Fludrocortisone depressed plasma norepinephrine in normal subjects but to a lesser degree than it depressed renin activity or urinary aldosterone excretion. Sympathetic nervous reactivity (defined as upright/supine plasma norepinephrine) was decreased more than supine plasma norepinephrine. Pretreatment supine plasma norepinephrine (but not plasma renin activity or aldosterone excretion) correlated with blood pressure changes during fludrocortisone dosing, which suggests participation of the sympathetic nervous system in the blood pressure elevations reported during exogenous steroid administration or primary aldosteronism. Suppression of sympathetic nervous activity and reactivity by fludrocortisone tends to explain its limited usefulness in patients with autonomic dysfunction and postural hypotension.

Adolescent↗