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Biomedical subjects

P I Korner

Publications and source records attributed to P I Korner.

At least 19 recordsLinked to original sources
PubMed1979

Effect of 6-hydroxydopamine on blood pressure and heart rate responses to intracisternal clonidine in conscious rabbits.

The effects of intracisternal injection (i.c.i.) of clonidine (1 microgram kg-1) on blood pressure and heart rate were studied in conscious rabbits with an implanted catheter in the cisterna magna. Each animal was studied under control conditions and 7 days after i.c.i. of 6-hydroxydopamine (6-OHDA) (1 microgram kg-1; n = 10) or ascorbic acid vehicle (n = 6). In the control experiments blood pressure and heart rate began to fall 1--2 min after i.c.i. of clonidine, with maximum falls at 10--20 min averaging 18 +/- 2 mmHg and 45 +/- 8 b/min and almost complete recovery by 90 min. After vehicle pretreatment neither response was significantly altered. After 6-OHDA the early component of the bradycardia was abolished and only a late fall in heart rate developed 30 min after i.c.i. clonidine. The magnitude of the hypotension was unaffected but the onset was slightly delayed, probably owing to the abolition of the bradycardia. The dose of 6-OHDA reduced spinal cord catecholamines to about 20% of the level observed after vehicle. Central catecholaminergic pathways are thus important in the early predominantly vagal component of the clonidine induced bradycardia, but play little role in the hypotensive response.

Animals↗
PubMed1979

Relative contributions of aortic and carotid sinus baroreceptors to the baroreceptor-heart rate reflex of the conscious rabbit.

Conscious rabbits with previously implanted perivascular balloons for altering blood pressure were studied before and 6 days after: (i) sham-operation (n = 6); (ii) section of carotid sinus nerves alone (n = 7); (iii) section of aortic nerves alone (n = 5); and (iv) combined sino-aortic denervation (n = 5). Sigmoid mean arterial pressure (MAP)-heart period (HP) baroreflex curves were derived and were characterized by: (i) the HP range (HPR) between upper and lower plateau levels; (ii) the median blood pressure (BP50); and (iii) the average gain (G). Resting MAP and HP and the 3 baroreflex parameters were not altered significantly 6 days after sham-operation. After section of the carotid sinus nerves alone resting MAP and BP50 rose by 18 +/- 2.6 mm Hg, resting HP fell by 31 +/- 4.2 msec, whilst HPR and G fell to about 45% and 20 % respectively of initial preoperative control. After cutting the aortic nerves alone there was a similar fall in resting HP as after carotid denervation. However, the rises in resting MAP and BP50 were only about half of those observed after carotid denervation (P < 0.05) and the changes in HPR and G to 65% and 58% of control respectively were also less marked (P ¿ 0.01). The aortic baroreceptor zone also exerted smaller effects on the sympathetic efferent component of the baroreflex HP response. Despite the different effects exerted by each zone on the reflex parameters there was little difference in threshold pressure for producing cardiac slowing. After combined sino-aortic denervation there was a similar rise in resting MAP (19 mm Hg) as after carotid sinus denervation alone, but there was more marked tachycardia, with a fall in resting HP of 82 msec (P < 0.001) and both resting and baroreflex-mediated vagal tones were completely abolished. The small residual pressure-determined HP changes of about 8 msec were entirely sympathetic and probably mediated through cardiopulmonary baroreceptors.

Animals↗
PubMed1979

Pindolol pharmacokinetics in relation to time course of inhibition of exercise tachycardia.

1 Pharmacokinetics of pindolol were studied in normal subjects given 5, 10 and 20 mg orally and 3 mg i.v. Plasma half time was 2.9 +/- 0.3 (s.e. mean) h for both routes; peak drug levels occurred 1--2 h after ingestion and bioavailability was 53%. Plasma protein binding was 38% and was independent of plasma concentration; the drug was not concentrated in the red cell. 2 Work-heart rate regression lines were calculated from resting heart rate and three grades of 'steady-state' exercise standardized for the maximum work capacity (Wmax) of each subject. The equation was characterized by slope and HR50 (calculated heart rate at 0.5 Wmax). 3 After giving 5 mg i.v. pindolol to produce maximum cardiac beta-adrenoceptor blockade there were differences in inhibition of resting heart rate, slope, HR50 and maximum heart rate suggesting differences in sympathetic components. However, estimates of the degree of inhibition were closely similar for each variable when determined before and after atropinization indicating that the accuracy of estimation was independent of the level of vagal activity. 4 After oral pindolol peak inhibition of resting heart rate, slope and HR50 coincided with peak plasma concentration. Peak reduction of resting heart rate was greatest at the lowest dose, but inhibition of slope and HR50 were similar at all doses. 5 The different heart rate parameters recovered at different rates. After 24 h slope had returned to control, and the residual inhibition of HR50 reflected residual beta-adrenoceptor blockade of resting heart rate, as demonstrated by a shift in isoprenaline-heart rate relationship. 6 Inhibition of HR50 and other exercise parameters were 20% less in the concentration range 5--20 ng/ml than peak inhibition obtained in the range 21--160 ng/ml. The higher potency of pindolol compared with propranolol can be accounted for by the difference in protein binding.

Adult↗
PubMed1979

Absorption and excretion of rapid and slow release oxprenolol and their effects on heart rate and blood pressure during exercise.

1. Plasma concentrations and heart rate and blood pressure effects of 160 mg oxprenolol as standard rapid release (RR) and slow release (SR) tablets were compared in healthy volunteers. Peak plasma concentrations were lower with SR tablets than with RR tablets and the peak was delayed. 2. Absorption of oxprenolol was described adequately by first order kinetics with both preparations. The apparent half-life of absorption was 0.40 h with RR and 2.4 h for the SR formulation. The apparent elimination half-life of oxprenolol was about 2 h. Relative bioavailabilities of the two formulations were similar. 3. The effectiveness of oxprenolol RR and SR were assessed by their effects on heart rate in severe exercise (EHR) and also by their effects on blood pressure at rest and during exercise. 4. Maximum reductions in these variables coincided with peak oxprenolol concentrations. The effects on EHR and blood pressure parameters had a distinct time course but there was no difference between the time course of inhibition of each variable for the two formulations over 24 h.

Adult↗
PubMed1979

Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.

1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance.

Angiotensin II↗
PubMed1979

Arterial and cardiopulmonary baroreceptor and chemoreceptor influences and interactions on ear sympathetic nerve discharge in the rabbit.

1. The effects of changing intravascular pressures on integrated ear sympathetic nerve activity (ESNA) were studied in anesthetized artificially ventilated rabbits by inflating aortic and inferior vena caval perivascular balloons under conditions of normal arterial Po2 and during arterial hypoxia. 2. At normal Po2 ESNA was unaffected by arterial and cardiopulmonary baroreflex influences. The small inhibition of ESNA observed during rises in arterial pressure after vagotomy was also present after section of the carotid sinus and aortic nerves, and after cutting both vagi as well. 3. During hypoxia there was marked inhibition of ESNA, which was minimally influenced by vagotomy but abolished by section of the carotid sinus and aortic nerves, suggesting that it was chemoreceptor-mediated. There was a pressure-related rise in ESNA which was abolished by vagotomy and considered to be due to a central nervous chemoreceptor-cardiopulmonary baroreflex interaction.

Animals↗
PubMed1978

Cardiovascular and behavioral effects of intracisternal 6-hydroxydopamine in the rabbit.

Acute effects of 6-hydroxydopamine (6-OHDA, 400--900 microgram kg-1 intracisternally, i.c.i.) consisted of bradycardia and hypertension, maximal 2--3 h after injection and preceded after some doses by a phase of hypotension. This pattern was obtained in completely conscious rabbits and after propanidid and sodium pentobarbitone anesthesia. After 600 microgram kg-1 i.c.i. 6-OHDA the peak rise in blood pressure (25 +/- 3.8 mm Hg) was due to a rise in peripheral resistance involving particularly renal and intestinal beds. Suprapontine mechanisms contributed to both hypertension and bradycardia. Giving pontine rabbits 6-OHDA elicited a short-latency fall in blood pressure, resembling the hypotensive phase in intact animals. Chronic effects 7 days after 600 microgram kg-1 included a rapid loss of 10% of body weight associated with reduction in food and water intake. To avoid secondary circulatory effects the rabbits were artificially fed, halving the weight loss. At 7 days blood pressure had fallen by 7.4 +/- 2.3 mm Hg probably owing to this residual weight loss. From experiments involving administration of phenotolamine and clonidine in intact rabbits and the responses of pontine animals it is likely that both descending and ascending catecholaminergic pathways have inhibitory effects on blood pressure, though some of the pathways may also be excitatory. Absence of specific chronic circulatory changes may be due to compensation through parallel pathways involving other transmitters.

Anesthesia↗
PubMed1978

Effect of d,l-propranolol on renal sympathetic baroreflex properties and aortic baroreceptor activity.

Sigmoid renal baroreflex curves relating mean arterial pressure to integrated renal sympathetic nerve activity were obtained in anaesthetized rabbits with previously implanted balloons to raise and lower blood pressure. Propranolol was infused to reach plasma levels averaging 324 ng/ml. This reduced blood pressure by 9.6 +/- 1.1 mm Hg, but had no effect on resting sympathetic discharge. Propranolol lowered the threshold of the renal baroreflex. Median blood pressure was reduced by 15.4 +/- 1.9 mmHg but there was no change in gain or sympathetic activity range. Thus, at a given blood pressure there was diminution of sympathetic discharge compared with control. Similar changes occurred after giving clonidine. However, "non-specific" produced by bleeding or nitroprusside infusion produced no resetting of the baroreflex curves, though the resting sympathetic discharge increased. The effects of propranolol (plasma levels 137 and 348 ng/ml) on arterial baroreceptor discharge were studied by deriving mean arterial pressure-integrated aortic nerve activity curves. Propranolol produced a reduction of aortic nerve discharge of about 7% of control. Single unit analysis showed a small reduction in firing frequency/sec near threshold, which was sufficient to explain the changes in integrated aortic nerve discharge. Since the changes in input from the aortic baroreceptors do not account for the reduction in threshold of the renal baroreflex, we conclude that the latter is due to the central nervous action of propranolol.

Animals↗
PubMed1978

Characterization of immunoreactive angiotensin in canine cerebrospinal fluid as Des-Asp1-angiotensin II.

1. Immunoreactive angiotensin II was measured in cerebrospinal fluid of four normal dogs. 2. The migration of this immunoreactive angiotensin II on polyacrylamide-slab gel electrophoresis was identical with the migration of the heptapeptide, Des-Asp1-angiotensin II, in each case. 3. The biological activity of the material from canine cerebrospinal fluid in a pressor bioassay was similar to that of Des-Asp1-angiotensin II. 4. The pressor activity of the canine material was abolished by treating the pressor bioassay rat with a competitive antagonistic analogue, Sar1-Ala8-angiotensin II. 5. The results suggest that the biologically active immunoreactive angiotension II present in normal canine cerebrospinal fluid is composed mainly of the heptapeptide fragment of angiotensin II, Des-Asp1-angiotensin II.

Angiotensin II↗
PubMed1978

The role of vasopressin in blood pressure control and in experimental hypertension.

1. The role of vasopressin in blood pressure control and in the pathogenesis of one-kidney Goldblatt hypertension in the conscious dog was investigated. 2. Infusion of synthetic arginine vasopressin to elevate plasma levels approximately five-fold caused bradycardia in normal dogs and increase in mean arterial blood pressure in dogs with pharmacological autonomic blockade. 3. A similar degree of elevation of plasma vasopressin concentration was observed after mild non-hypotensive haemorrhage. 4. Renal artery constriction in unilaterally-nephrectomized dogs caused a rise in plasma renin activity and only a doubling of plasma vasopressin concentration, but a marked rise in mean arterial blood pressure. 5. Vasopressin may play a role in normal cardiovascular homeostatic responses, but its role in the pathogenesis of this form of hypertension is unlikely to be significant.

Animals↗
PubMed1978

Guanethidine-induced vasodilatation in the rabbit, mediated by endogenous histamine.

1 The effects of guanethidine (0.5-4 mg/kg i.v.) on arterial pressure, hindlimb blood flow and hindlimb vascular resistance (HVR) were studied in unanesthetized rabbits subjected to "total" autonomic block. 2 Evidence that this response was mediated by histamine release was that (a) 3H-labelled histamine levels in the hindlimb venous blood rose substantially after guanethidine; (b) infusion of exogenous histamine caused an inhibition of the guanethidine-induced vasodilatation; and (c) competitive antagonism of the response was obtained with the H2-antagonist burimamide. 3 There was good correlation between the [3H]-histamine ;elease and the time course of the vasodilator response. Glyceryl trinitrate infusions that lowered HVR substantially, did not cause release of histamine. 4 Reserpine, desipramine and indomethacin pretreatment did not alter the vasodilator response to guanethidine. 5 The guanethidine vasodilator response was not influenced by the H1-antagonist mepyramine or by the other H2-antagonists, metiamide or cimetidine. The vascular receptors stimulated by endogenous histamine may be distinctive from those stimulated by exogenous histamine, or the action of guanethidine may involve greater production of histamine at an intracellular site that is more readily reached by burimamide than by the other H2-antagonists.

Animals↗
PubMed1978

Cardiovascular-respiratory reflex interactions between carotid bodies and upper-airways receptors in the monkey.

The carotid bodies were stimulated in the anesthetized pig-tailed macaque monkey (Macaca nemestrina) using i) brief injections of cyanide or CO2-equilibrated bicarbonate solution into a common carotid artery, and ii) longer perfusion with hypoxic hypercapnic blood in vascularly isolated chemoreceptor preparations. In spontaneously breathing animals, brief stimulations of the chemoreceptors consistently caused an increase in pulmonary ventilation, bradycardia, and an increase in femoral vascular resistance. When the same chemoreceptor stimulus was superimposed during the apneic period, reflexly evoked by stimulating either the central ends of the superior laryngeal nerves or the nasopharynx, the respiratory stimulation was absent or minimal, but the bradycardia and vasconstriction were greatly enhanced and exceeded the summed responses of separate stimulation of the chemoreceptors and one or the other of the upper-airways inputs. With sustained stimulation of the carotid bodies, hyperventilation, tachycardia, and femoral vasodilatation occurred due to overriding respiratory mechanisms. When superior laryngeal nerve stimulation was superimposed on this response, apnea occurred and tachycardia was reversed to bradycardia, and femoral vascular resistance increased above resting level. The interaction of autonomic responses resulting from chemoreceptor stimulation and from increases in the upper-airways inputs are qualitatively similar in the monkey and in subprimate species. Those involving specifically cardioinhibitory vagal responses are, in part at least, dependent on mechanisms related to the concomitant changes in respiration.

Animals↗
PubMed1977

Baroreflex "resetting" by arterial hypoxia in the renal and cardiac sympathetic nerves of the rabbit.

1. Renal and cardiac sympathetic baroreflex functions were studied in sodium pentobarbitone anaesthetized rabbits given succinylcholine, during constant artificial ventilation with air and with hypoxic gas mixtures. Mean arterial pressure (MAP) was raised and lowered between values of 40 and 140 mm Hg by means of aortic and vena caval periovascular balloons and integrated sympathetic nerve activity (SNA) was recordered. 2. The relationship between MAP and SNA was sigmoid, with upper and lower plateau levels. The curves were defined by calculating median blood pressure, SNA Range and reflex gain. In both renal and cardiac sympathetics section of the carotid sinus and aortic nerves completely abolished the MAP-related changes in SNA. 3. The renal baroreflex curves were reset from control levels during hypoxia. Median blood pressure increased, as did SNA Range and gain. These effects were due to central interactions between arterial baroreceptor, arterial chemoreceptor and vagal afferent activity. 4. The cardiac sympathetic baroreflex curves were shifted in the opposite direction from control with reduction in median blood pressure, SNA Range and reflex gain. These changes were due to chemoreceptor-arterial baroreceptor interactions. 5. Arterial hypoxia thus evokes a differentiated pattern of baroreflex resetting in the renal and cardiac sympathetic montoneuron pools with differing changes in neural response range and sensitivity to arterial pressure changes.

Animals↗
PubMed1977

Autonomic blockade and the Valsalva maneuver in patients on maintenance hemodialysis: a hemodynamic study.

Hemodynamic studies were performed at two levels of dietary sodium intake (10 mmoles/day and 100 mmoles/day for 14 days) in a group of patients (with retained kidneys) on chronic hemodialysis. Plasma renin activity and aldosterone, plasma, and extracellular fluid (ECF) volumes were measured while the patient were at rest. Cardiac output, mean intraarterial pressure, and the calculated total peripheral resistance index were recorded while the patients were at rest and during acute "total" autonomic blockade. On the sodium diet of 10 mmoles/day, normotensive and hypertensive patients had similarly low total blood volumes, low-normal ECF volumes, and similar levels of plasma renin and aldosterone. The resting cardiac output was increased in both groups, but the total peripheral resistance was increased only in the patients with hypertension, in whom peripheral resistance was inappropriately high for the degree of anemia. Six hypertensive patients were studied on both diets. The resting mean arterial pressure was greater on the sodium diet of 100 mmoles/day than on the 10 mmoles/day diet, accompanied by increased in plasma volume, extracellular fluid volume, and cardiac output, but no change in peripheral resistance. During autonomic blockade on either diet, there was a marked fall in blood pressure in the patients with hypertension. This was mainly due to a fall in peripheral resistance which reached levels similar to those seen in the normotensive patients whose resistance was unaltered by blockade. Autonomic factors appear to contribute to the elevated peripheral resistance of hypertensive dialysis patients. In these patients, the effect of a high sodium diet, at least over the time-scale studied here, is to increase blood pressure and cardiac output, without the change in peripheral resistance expected from autoregulation.

Adult↗
PubMed1976

Double-blind factorial trial of prindolol and hydrochlorothiazide in hypertension.

The antihypertensive actions of the beta-adrenergic blocking agent, prindolol, and of the diuretic, hydrochlorothiazide, were analysed in a double-blind randomized 2 X 2 factorial trial in 16 patients. There were four eight-week phases in which patients received prindolol alone, hydrochlorothiazide alone, prindolol plus hydrochlorothiazide in combination, and no treatment. Both drugs were given in fixed doses: prindolol, 10 mg three times per day; hydrochlorothiazide, 50 mg per day. Blood pressure was measured weekly, alternately at the outpatient clinic and at home. Supine mean arterial pressure (MAP) in resting patients fell from 127 mm Hg in the placebo phase to 117 mm Hg with hydrochlorothiazide alone, 116 mm Hg with prindolol alone, and 111 mm Hg with the combination of prindolol and hydrochlorothiazide. (The standard error of difference between treatments was +/-3-58). A mean factorial effect of -7 mm Hg for hydrochlorothiazide (P less than 0-01) and -8 mm Hg for prindolol (P less than 0-01) was obtained, and the two drugs acted in an additive manner. The effects on standing blood pressure in resting patients were similar. No serious side effects were noted.

Adult↗
PubMed1976

Valsalva vasoconstrictor reflex in human hypertension in after beta-adrenoreceptor blockade in conscious rabbits.

1. A Valsalva-like manoeuvre was used to elicit graded rises in total peripheral resistance (TPR) in conscious rabbits. The rises were reflex and mediated through sympathetic constrictors. Propranolol infused at different rates reaching plasma concentrations up to 240 (SEM 33) ng/ml had no effect on this reflex but reduced mean arterial pressure. However, the response was attenuated by clonidine in a dose-dependent manner. 2. Valsalva manoeuvres were used to elicit graded sympathetically mediated rises in TPR index in twenty-nine subjects with mean arterial pressure ranging from 75 to 165 mmHg. Absolute sensitivity of the constrictor response increased with rising resting TPR index, resulting in some enhancement of constrictor responses in the hypertensive subjects. It seems likely that non-autonomic factors (e.g. vessel structure) rather than hyperactive neural constrictor effects are involved in the enhanced constrictor responses in essential hypertension.

Adrenergic beta-Antagonists↗