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Biomedical subjects

H R Keiser

Publications and source records attributed to H R Keiser.

At least 127 records · Page 7Linked to original sources
PubMed1985

Clonidine suppression testing in essential hypertension.

To assess the contribution of sympathetic outflow to blood pressure in patients with essential hypertension, we measured blood pressure and plasma norepinephrine responses to clonidine, an antihypertensive agent that decreases central sympathetic outflow, in 44 patients and in 41 normotensive control subjects of similar age. Among the hypertensive patients, the resting level of plasma norepinephrine was significantly related to the decrease in mean arterial pressure 3 hours after a single oral dose of clonidine 300 micrograms (r = 0.62, p less than 0.001). The magnitude of the depressor response in the patients also was correlated significantly with the decrease in plasma norepinephrine after clonidine (r = 0.60, p less than 0.001). These results suggest that increased sympathetic outflow plays a pathophysiologic role in some patients with essential hypertension.

Adult↗
PubMed1984

[3H]nitrendipine binding to adrenal capsular membranes.

The physiologic regulation of aldosterone secretion is dependent on extracellular calcium and appears to be mediated by increases in cytosolic free calcium concentration in the zona glomerulosa cell. A specific role for voltage-dependent calcium channels was suggested by previous studies with the calcium channel antagonist verapamil. We therefore studied the [3H]nitrendipine calcium channel binding site in adrenal capsules. These studies revealed a single class of saturable, high affinity sites with KD = .26 +/- .04 nM and Bmax = 105 +/- 5.7 fmol/mg protein. Specific binding of [3H]nitrendipine was inhibited by calcium channel antagonists with potencies nitrendipine = nifedipine much greater than verapamil, while diltiazem had no inhibitory effect. In the rat, binding sites for [3H]nitrendipine were located in the adrenal capsule and medulla and were undetectable in the zona fasciculata. Physiologic studies with collagenase-dispersed adrenal glomerulosa cells demonstrated that nifedipine selectively inhibited angiotensin-II and potassium-stimulated steroidogenesis. These observations suggest both a pharmacologic and physiologic role for the nitrendipine binding site in aldosterone production.

Adrenal Medulla↗
PubMed1984

Pressor and depressor responses after cholinergic blockade in humans.

To determine whether cholinergic mechanisms contribute to blood pressure responses during arterial baroreflex inhibition and stimulation, we assessed the effects of atropine on pressor and depressor responses during and after release of the Valsalva maneuver, upon administration of intravenous phenylephrine and nitroglycerin, and during neck suction in 12 healthy people. Atropinization augmented the depressor response during the Valsalva maneuver (269%), the pressor response after release of the maneuver (544%), the pressor response to phenylephrine (109%), and the depressor response to nitroglycerin (76%), whereas the depressor response to externally applied neck suction was attenuated or abolished in all subjects. Cardiac output as indicated by impedance cardiography was unchanged during carotid baroreceptor stimulation. The results are best explained by inhibition by atropine of compensatory cholinergic heart rate, vasodilator, and negative inotropic responses.

Adult↗
PubMed1984

Prostaglandin E2 but not F2 alpha restores the natriuretic response to acetylcholine in indomethacin-treated dogs.

Renal arterial infusion of acetylcholine (ACh) (40 micrograms/min) produces a natriuresis, diuresis, and an increase in renal plasma flow (RPF) without a change in glomerular filtration rate (GFR) or renin secretory rate (RSR). The present study was designed to examine the role of prostaglandins in this natriuretic response to ACh. In dogs pretreated with indomethacin (Indo) (5 mg/kg, i.v.), an inhibitor of prostaglandin synthesis, renal arterial infusion of ACh produced an increase and then a decline in urinary flow and sodium excretion accompanied by a progressive fall in GFR and RPF and a progressive increase in RSR. Renal arterial infusion of PGE2 (1.9 micrograms/min) but not PGF2 alpha (1.9 micrograms/min) before and during the infusion of ACh restored the diuretic and natriuretic response to ACh in Indo-treated dogs. Renal arterial infusion of bradykinin (BK) (3 micrograms/min) in Indo-treated dogs produced a diuresis and natriuresis similar to that produced by PGE2; renal arterial infusion of BK, however, did not restore the diuretic and natriuretic response to ACh in Indo-treated dogs. The data suggest that Indo shortens the diuretic and natriuretic response to ACh by inhibiting synthesis of prostaglandins, possibly PGE but not PGF. The data further suggest that PGE2 restores the diuretic and natriuretic response to ACh in Indo-treated dogs through a specific action rather than by its action as a renal vasodilator.

Acetylcholine↗
PubMed1983

Bradykinin reverses the effect of opiates in the gut by enhancing acetylcholine release.

Four naturally occurring peptides of the kinin family, bradykinin, lysylbradykinin, methionyllysylbradykinin, and polisteskinin reverse the inhibitory effect of morphine, metenkephalin, and epinephrine on the electrically stimulated guinea pig ileum longitudinal muscle myenteric plexus preparation. Bradykinin, the most potent kinin, enhances the release of acetylcholine in the gut, and its reversal of the opiate inhibitory effect is blocked by the anticholinergic drug, hyoscine.

Acetylcholine↗
PubMed1983

Abdominal vagotomy does not modify endotoxic shock in rats.

Bilateral subdiaphragmatic vagotomy does not improve the clinical course nor the survival of Sprague-Dawley rats injected intravenously with E. coli lipopolysaccharide. These results show that whatever peripheral signals are elicited by endotoxin to generate the centrally mediated hypotensive response, they are not conveyed to the central nervous system by abdominal vagal afferent fibers.

Animals↗
PubMed1983

Plasma and urinary catecholamines during the human ovulatory cycle.

We measured plasma catecholamine concentrations and urinary catecholamine excretion during the ovulatory cycle in six healthy women. Plasma norepinephrine was consistently at its lowest during the follicular phase of the cycle. Plasma norepinephrine began to increase about 2 days before ovulation and continued to increase after ovulation, so that the average luteal phase NE concentration was significantly higher than the average follicular phase concentration (217 versus 143 pg/ml, p less than 0.001). Urinary norepinephrine excretion showed a similar but attenuated pattern. The results suggest that sympathetic neural activity changes with the phase of the ovulatory cycle. Cyclic patterning of plasma norepinephrine is one of many factors which should be considered in the design and analysis of studies which use plasma norepinephrine as an indicator of sympathetic neural activity in human disease states.

Adult↗
PubMed1983

Effects of injected sympathomimetic amines on plasma catecholamines and circulatory variables in man.

We measured blood pressure, heart rate (HR), and plasma catecholamine responses to a 5-minute infusion of 0.3 mg/kg d-amphetamine (d-A) and to graded bolus injections of tyramine (Tyr) to a similar increment in systolic pressure (BPs), in 9 and 7 healthy people, respectively. Both sympathomimetic agents dramatically increased BPs (mean increases peaking at 39 and 36 mm Hg for d-A and Tyr), associated with increased plasma norepinephrine (NE) (224 and 149 pg/ml) but unassociated with changes in plasma epinephrine or HR. The time course of BPs and NE responses to Tyr was much shorter than to d-A, but the pattern was similar. The results are consistent with the hypotheses that both agents increase BPs via increased synaptic cleft NE, and that circulating plasma NE reflects "spillover" from the cleft into the general circulation.

Blood Pressure↗
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↗
PubMed1983

Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension.

We infused tracer-labeled l-[3H]-norepinephrine, d-[14C]norepinephrine, and d,l-[3H]-isoproterenol simultaneously into patients with essential hypertension and into normotensive control subjects, in order to determine whether abnormalities in the disappearance kinetics of these substances characterized the hypertensive patients. The mean preinfusion venous plasma norepinephrine concentration was somewhat higher in the hypertensive group (260 vs. 194 pg/ml, P = 0.06), but the groups did not differ in the disappearance kinetics of l- or d-norepinephrine or of isoproterenol. Preinfusion plasma norepinephrine was significantly positively correlated with calculated spillover rates in both the hypertensive and normotensive groups, but not with norepinephrine clearances. The d/l ratio in plasma norepinephrine was the same as in the infusate during and after the infusion, even after pretreatment with the neuronal norepinephrine uptake blocker, desipramine. Because isoproterenol is not taken up by nerve endings, the ratio of [3H]isoproterenol to l-[3H]norepinephrine increased after the infusion ended. This increase was almost completely abolished by pretreatment with desipramine. These results indicate that (a) increased plasma norepinephrine levels seen in some patients with essential hypertension result from increased sympathetic neural activity and not from decreased clearance of norepinephrine, (b) changes in the isoproterenol/norepinephrine ratio after simultaneous infusion of both provide an index of neuronal norepinephrine uptake in man, and (c) neuronal norepinephrine uptake is not stereospecific.

Adult↗
PubMed1983

A case of episodic flushing and organic psychosis: reversal by opiate antagonists.

A woman had episodic attacks of flushing associated with severe skin, bone, and abdominal pain, accompanied by mood alterations and anxiety, and followed by an organic psychosis. These symptoms and signs could be induced by small doses of clonidine, L-5-hydroxytryptophan, pentagastrin, insulin, epinephrine, compound 48/80, methacholine, morphine, histamine, or d-tubocurarine. Skin testing showed abnormally sensitive mast cells and an exaggerated axon flare. Cimetidine initially prevented the attacks but became less effective after 18 months. Thyrotropin-releasing hormone stopped the skin pain whereas neurotensin reproduced the burning sensation in the skin without inducing the attack. Both the flush and the organic psychosis were reversed entirely by naloxone or naltrexone, and the hallucinosis could be reversed by vasodilators.

Adult↗
PubMed1982

Naloxone attenuates the hypotension induced by Hageman factor.

The hypotension induced in the pentobarbital anesthesized rat by the i.v. administration of an active Hageman factor fragment (Hff) is significantly attenuated by naloxone. This effect is specific because the opiate antagonist does not modify the hypotension elicited by rat urinary kallikrein, bradykinin or nitroglycerin. These results suggest that the contact activation of endogenous Hageman factor could result in the generation of vasoactive opioid peptides derived from circulating large molecular weight precursors.

Animals↗