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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Abnormal norepinephrine release in uremia.

Sympathetic nervous activity, which we defined as the relative rate of appearance of norepinephrine (NE) in plasma, was investigated in normal men (control) and uremic patients with two-step steady-state cold NE infusions. Both basal venous NE and the NE metabolic clearance rate (CNE, calculated from the infusion rate and the steady-state increment in venous NE) were higher in patients than in controls. The calculated appearance rate of NE in venous plasma (CNE X basal NE) was much higher in the patients, suggesting increased NE release and therefore sympathetic nervous hyperactivity in these patients.

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.

Cardiovascular hormonal effects of circulating norepinephrine.

The hormonal effects of circulating norepinephrine (NE) were evaluated with two-step NE infusion studies in normal volunteers. At an infusion rate that increased plasma NE 2.5-fold (approximately equivalent to the change from supine to upright posture), there were small but consistent increases in diastolic pressure (+5 mm Hg) and plasma renin activity (+13%).

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.

Protective effects of beta blockade on pulmonary function when intracranial pressure is elevated.

Intracranial pressure (ICP) was increased by hyperosmolar intracerebral infusion in dogs and the cardiopulmonary and catecholamine (CA) responses followed for 4 h. Increased ICP evoked persistent increases in endogenous CAs, pulmonary vascular pressures, pulmonary blood volume, and venous admixture. Other dogs similarly monitored were treated with a beta-blocking dose of propranolol 25 min after the onset of increased ICP.

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.