Search PubMed⌕ Search

Biomedical subjects

J E Zehr

Publications and source records attributed to J E Zehr.

At least 19 recordsLinked to original sources
PubMed1994

Atrial natriuretic factor in the freshwater turtle Pseudemys scripta: a partial characterization.

The presence of natriuretic and vasorelaxant materials in the atria and ventricles of a Chelonian reptile, the freshwater turtle Pseudemys scripta, was verified and the active substance partially characterized. Crude atrial and ventricular extracts were acutely natriuretic and diuretic when administered to anesthetized rats increasing sodium excretion 23.5 +/- 7.9 and 5.11 +/- 18 microM Na/10 min/mg extract, respectively. Although atrial extracts were relatively more natriuretic than ventricular extracts, the total natriuretic content of ventricular extracts was approximately twofold greater. Moreover, partially purified atrial extracts were found to relax precontracted isolated rat aortic ring segments and exhibited immunoreactivity to mammalian ANP antisera. Also, the natriuretic and immunoreactive substance was purified further by size exclusion chromatography and a molecular weight of 3-5 kDa was determined. Using the bovine adrenal glomerulosa ANP receptor, this partially purified natriuretic substance displayed an apparent binding affinity similar to that of mammalian ANP. Finally, in order to demonstrate that this reptile is physiologically responsive to ANP, synthetic rat ANP (10 micrograms/kg) was shown to decrease arterial pressure in conscious turtles from a control value of 37.2 +/- 5.2 to 30.3 +/- 2.7 mm Hg. These data demonstrate that unlike other non-Chelonian reptiles, both the atria and the ventricles of this Chelonian reptile synthesize and store substantial levels of biologically active ANP-like materials, and further, that ANP is a highly conserved and primitive cardiac hormone.

Animals↗
PubMed1992

Isolation and purification of a vascular hyperreactivity factor from rabbit kidney cortex.

A compound capable of amplifying the threshold pressor response to norepinephrine (NE) was obtained from rabbit kidney cortex. This compound was purified and characterized using a series of techniques including gel filtration, ion exchange chromatography, preparative electrofocusing, HPLC, FAB mass spectrometry (FAB-MS), and Fourier transform infrared spectrometry. From this, an acid/heat stable (6N HC1, 160 degrees C, 24 hours), low molecular weight (ca 147) compound with a strong (+) charge density (Pi greater than 10) was identified. When injected into assay rats (i.v.), this compound amplified the pressor response to fixed doses of NE. Taken together, this compound exhibits nearly identical characteristics (i.e. acid/heat stability, structure, charge and biologic activity to the naturally occurring polyamine spermidine (SPD-145.6 daltons). Moreover, bolus injections of SPD (10 micrograms, i.v.) amplified the pressor response to NE over a range of doses from 5-25 ng.

Animals↗
PubMed1990

Spontaneous rhythmic contractile behaviour of aortic ring segments isolated from pressure loaded regions of the vasculature.

STUDY OBJECTIVE: The aim was to study contractile responses of segments of rat arteries taken from pressure loaded and pressure protected regions and to examine the role of endothelial derived factors on the spontaneous activity of pressure loaded ring segments. DESIGN: Rats were subjected to complete aortic coarctation between the origins of the renal arteries and allowed to recover for 8 d. After 8 d arterial pressures were measured in awake animals from the pressure loaded and pressure protected regions simultaneously. Ring segments (2-3 mm) were taken from the two regions and mounted in a tissue bath for isometric force measurements. Similar studies were conducted in sham animals and in animals in which the kidney distal to the coarctation had been removed. EXPERIMENTAL MATERIAL: Female Sprague-Dawley rats, weight 200-250 g, were used. MEASUREMENTS AND MAIN RESULTS: Eight days after coarctation mean aortic pressure proximal to the occlusion was 168(SEM 1.29) mm Hg (n = 104) while distally it was 38(2.42) (n = 40). Of the rings tested 96% showed spontaneous rhythmic activity, having a mean frequency of 3.94(0.17) cycles.min-1. Spontaneous activity was not present in the pressure protected segments taken from the same animals. Rats with the distal kidney removed (n = 25) failed to become hypertensive and similarly prepared ring segments failed to show spontaneous rhythmic activity. Prior removal of the endothelial layer had no effect on the spontaneous contractile responses in pressure loaded segments. Histological examination showed that the media to lumen ratio was increased in coarcted rats in both pressure loaded and pressure protected regions compared to similar regions in sham operated animals. CONCLUSIONS: Pressure loaded arterial segments show spontaneous contractile activity when compared to sham segments by mechanisms not dependent on endothelial derived factors. The increase in pressure proximal to the occlusion is dependent on the renin-angiotensin system, since pressure was not increased when the distal kidney was removed. We hypothesise that the chronic pressure load induces fundamental changes in membrane permeability which leads to spontaneous contractile activity.

Acetylcholine↗
PubMed1989

Autonomic modulation of ultradian blood pressure and heart rate oscillations in dogs.

Autonomic receptor modulation of ultradian oscillations of blood pressure and heart rate was studied in telemetered free-running dogs. Data, analyzed for their harmonic content by fast Fourier transform (FFT) methods, indicated that ultradian and circadian oscillations of 22.9 +/- 2.5 and 10.5 +/- 0.9 (SD) mmHg, respectively, were present. The average principal frequency for the ultradian oscillations in 12 dogs was 0.760 +/- 0.11 cycles/h for arterial pressure and 0.808 +/- 0.10 for heart rate. Atropine had no effect on periodicity of either arterial pressure or heart rate. Metoprolol, a beta 1-antagonist, or hexamethonium, a ganglionic blocker, significantly reduced the power of both arterial pressure and heart rate (P less than 0.05), whereas the primary frequencies of both were unchanged. Prazosin, an alpha 1-blocker, sharply reduced arterial pressure power (P less than 0.05) and increased the power of heart rate (P less than 0.05), demonstrating that it is possible to uncouple arterial pressure oscillations from influences of heart rate. We conclude that the sympathetic limb of the autonomic nervous system is primarily responsible for these oscillations and that vagal influences on the heart partially dampen these rhythms.

Activity Cycles↗
PubMed1988

Statistical criteria for using short-term measurements as an index of 24-hour mean arterial pressure in unanesthetized unrestrained dogs.

This study assessed the statistical validity of short time-interval measurements as estimators of true 24 hour mean arterial pressure in unanesthetized, unrestrained dogs. 24 hour intra-arterial pressure recordings were obtained using a stable FM telemetry system. The 24 hour pressure measurements approximated a normal distribution whose variance was inversely related to the selected averaging interval. Given the variance of a normal distribution one can calculate the 95% confidence interval for any single random measurement. Conversely the number of random samples necessary to be within a prescribed confidence interval can be determined. In this study, the 95% confidence interval for a single, random 30 minute arterial pressure average was calculated to be 11.2 mmHg. Only 4.8 +/- 1.4% of 480 individual 30 minute arterial pressure measurements fell beyond this confidence interval. These outlying values were distributed throughout the 24 hour period. The data suggest that randomly chosen short time-interval measurements may be a valid index of true 24 hour mean pressure if the average variance of a population is known and confidence intervals are defined.

Animals↗
PubMed1986

Effect of autonomic agents on renin release in the turtle, Pseudemys scripta.

Experiments were conducted in the freshwater turtle, Pseudemys scripta, to study the effect of autonomic agents on the control of renin in this primitive species. The unique finding in these studies was that, unlike mammals, isoproterenol infusion fails to increase renin activity even though heart rate and arterial pressure patterns indicated that systemic responses were similar to that in mammals. On the other hand, acetylcholine (ACh) infusion resulted in a prompt threefold elevation (P less than 0.01) of renin activity. This response was blocked by propranolol but not atropine. Other experiments demonstrated that ACh elicited a prompt elevation of circulating norepinephrine and epinephrine in these turtles and led to the hypothesis that the renin response to ACh was secondary to the release of endogenous catecholamines. This hypothesis was supported by the fact that, in reserpinized turtles, ACh failed to elicit the usual renin response. Further evidence stemmed from the fact that epinephrine administration led to a prompt fourfold increase (P less than 0.01) in renin, which could be blocked by propranolol. On the other hand, phenoxybenzamine failed to block the response under identical conditions. Taken as a whole, these data suggest that in this primitive species renin activity is elevated by endogenous catecholamines even though isoproterenol, a classical beta-adrenergic agonist, is without effect. These data illustrate again the need for caution when assuming analogy when comparing responses in primitive species with that of mammals.

Acetylcholine↗
PubMed1985

Renin release in turtles: effects of volume depletion and furosemide administration.

To gain insight into the phylogenetic history of mechanisms controlling renin release, we conducted studies in the freshwater turtle Pseudemys scripta. Maneuvers known to stimulate renin release in mammals were evoked in the turtle, and the response was compared with that in mammals. Cumulative hemorrhage (30% blood vol) in anesthetized turtles failed to increase renin even though arterial pressure was reduced to 50% of control. An even more severe hemorrhage (60% blood loss) or hypotension induced by nitroprusside infusion in unanesthetized turtles also failed to evoke an enhanced level of renin. However, under identical experimental conditions, a 15% blood loss in rats increased renin at least fourfold (P less than 0.01). In other studies 48 h of furosemide administration in awake turtles increased renin more than threefold (P less than 0.05) and were accompanied by concomitant reductions in plasma sodium and potassium (P less than 0.05). The general conclusions drawn from these studies is that renin secretion in this primitive vertebrate is similar to that in mammals with respect to renal tubular and electrolyte mechanisms, but unlike all mammals tested these turtles do not possess an intrarenal baroreceptor component in renin control.

Animals↗
PubMed1985

The influence of renal sympathetic nerves on renal hemodynamic and renin responses during hypercapnia in dogs.

Studies were conducted in anesthetized dogs to examine the influence of the renal sympathetic nerves on renal hemodynamic and renin responses during controlled hypercapnia. The dogs were subjected to unilateral denervation and tested for their responses to hypercapnia induced by inhalation of 15% CO2 in air. Simultaneous measurements of the responses from both the denervated and innervated kidneys allowed an assessment of the influence of the renal nerves on the responses during acute hypercapnia. The data indicate that reductions in renal blood flow and glomerular filtration rate and increases in renin of the renal vein during respiratory acidosis are dependent, in part, on the presence of intact renal nerves. Other factors, however, are probably also present.

Animals↗
PubMed1984

Inhibition of renin release following left circumflex bradykinin injection in dogs.

We examined the renin secretory response to bradykinin (BK) injection into the left circumflex coronary artery (LCx) in dogs. Studies were conducted in anesthetized, carotid sinus denervated dogs which had been maintained on a low sodium diet. A 25 ga needle was inserted into the LCx for injection of BK (0.15 micrograms/kg). The rate of renin secretion (RS) was obtained during a 30 min control period, at 5 min after a non-hypotensive hemorrhage (10 ml/kg), at 1, 3 and 5 min after BK injection and at 15 min after the reinfusion of withdrawn blood. Four series of studies were conducted. Series I: BK injection into the LCx, Series II: saline injection into the LCx (sham), Series III: intravenous injection of BK, and Series IV: BK injection into the LCx in dogs with prior renal denervation. RS was suppressed by 80% (P less than 0.05) 5 min after injection of BK into the LCx. Saline injection (sham) into the LCx or intravenous BK administration did not inhibit RS. Furthermore, suppression of RS was not present in dogs with prior renal denervation. These results indicate that BK injection into the LCx causes a prompt reduction in the rate of RS and that this response is reflexively mediated by the renal nerves.

Animals↗
PubMed1984

Chemical structure of angiotensin in the turtle, Pseudemys scripta.

The chemical structure of angiotensin generated by incubating kidney extract with homologous plasma from the turtle, Pseudemys scripta, has been analyzed. The turtle angiotensin was proposed to be [Asp1, Val5, His9] ANG I by its amino acid composition and by its fluorescent peptide mapping. It was the same structure as angiotensin I in the ox and the sheep. The N-terminal amino acid of the turtle angiotensin was not blocked, unlike that of another reptilian angiotensin found in the snake, Elaphe climacophora.

Amino Acid Sequence↗
PubMed1984

Ultradian oscillations in blood pressure and heart rate in free-running dogs.

A long-term (14-24 h) telemetry recording of mean arterial pressure (MAP) and heart rate (HR) was obtained from conscious unrestrained dogs (n = 9) maintained in a closed environment. MAP and HR records were analyzed for their harmonic content by the fast Fourier transform method. The power spectral density functions of MAP and HR clearly revealed the existence of coherent ultradian rhythms of MAP and HR with a period of 1-2 h. HR and MAP are in phase and sustained during a 24-h period. To elucidate the nature of these rhythms, two additional studies were conducted (n = 4) in which clonidine (200 micrograms/kg) was administered systemically. In series I, a 7-h control period preceded the administration of clonidine, whereas in series II the order was reversed. Control (series I) and recovery (series II) periods were compared with a 0- to 7-h postinjection period. The results show that clonidine drastically and significantly reduces the amplitude of both MAP and HR oscillations for an average period of 7 h. This response was very consistent in both series and in all four dogs. These results implicate the central nervous system as the origin of these rhythms.

Animals↗
PubMed1984

Characterization of the renin-angiotensin system in the turtle Pseudemys scripta.

Studies were conducted in freshwater turtles Pseudemys scripta to define some characteristics of the renin-angiotensin system in this reptile. Dialyzed acid-treated kidney extract (1 g tissue per ml water) produced a prolonged pressor response in unanesthetized turtles, which was eliminated by boiling the extract or by pretreating the turtle with [Sar1, Ile8]angiotensin II. A rat pressor assay was employed because turtle angiotensin (ANG) was bound poorly by the anti-[Asp1, Ile5, His9]ANG I used in our radioimmunoassay. Kidney extract incubated with homologous plasma (pH 5.5 and 25 degrees C) produced a time-dependent pressor response in rats. The pressor activity of the product was eliminated by dialysis or by pretreating the rats with [Sar1, Ile8]ANG II. The pressor response in anesthetized turtles to ANG I was significantly reduced by captopril, whereas the ANG II response remained unchanged, thus demonstrating the presence of ANG-converting enzyme activity in these animals. We determined the velocity of turtle ANG formation at various dilutions of enzyme (kidney extract) or substrate (plasma). Turtle kidney extract incubated with homologous plasma displayed typical Michaelis-Menten kinetics. Finally we conducted experiments to determine whether a portion of turtle plasma renin exists in an inactive form. Trypsinization caused a slight increase in plasma renin activity (PRA), whereas acidification to pH 3.3 yielded a fourfold increase in PRA.

Angiotensin I↗
PubMed1983

Crystal-controlled telemetry system for long-term acquisition of physiological data.

A crystal-controlled telemetry system was developed for long-term high-reliability recording of blood pressure in unrestrained animals. The miniaturized transducer-transmitter system is powered by two lithium batteries that allow for more than 200 h of continuous recording of blood pressure before battery replacement. The total system has a flat frequency response of 0-25 Hz and a time stability of +/- 1 mmHg/day. Linearity is better than 0.5%. The high degree of dependability of the system permits us to perform continuous, unattended, around-the-clock recordings of pressure and heart rate in unrestrained animals. Very high dependability is achieved by the use of a novel piezoresistive blood pressure transducer and by the inherent stability of the crystal-controlled radio-frequency oscillator of the transmitter. The receiver is also crystal tuned to the measured transmitter frequency. This transmitter-receiver frequency locking ensures very reliable reception of the telemetered signal.

Animals↗
PubMed1983

Role of calcium in the interaction of alpha and beta adrenoceptor-mediated renin release in isolated, constant pressure perfused rabbit kidneys.

These experiments were designed to study the role of calcium in the modulation of renin secretion by alpha and beta adrenoceptors. Rabbit kidneys were isolated and single-pass perfused with a modified Ringer's solution. Renal perfusion pressure was precisely controlled by an electronic servocontrol system. Tubular events were minimized by ligation of the ureter before initiating the studies. Under these conditions the predominant factor modifying renin secretion was assumed to originate directly on the juxtaglomerular cells. Isoproterenol infused at 0.1, 0.5, 1.0 and 5.0 nM/min/g of kidney weight increased renin secretion in a dose-dependent manner whereas phenylephrine infused at identical molar doses did not. In addition, phenylephrine (5.0 nM/min/g of kidney weight) blocked the usual response to isoproterenol. Removal of calcium from the perfusing medium had no effect on either the response to isoproterenol or the lack of a response to phenylephrine. On the other hand, when calcium is removed from the perfusate or when D-600, a calcium channel blocker, is added to calcium-containing medium, phenylephrine failed to block the usual response to isoproterenol. We conclude that the suppression of beta adrenoceptor stimulation of renin release by alpha adrenoceptor agonists is calcium dependent by a final mechanism as yet undefined, but probably involving movement of calcium into the juxtaglomerular cells.

Animals↗
PubMed1982

Acute inhibition of renin release during left circumflex coronary occlusion in dogs.

We examined the reflex effect of brief left circumflex coronary artery occlusion (CAO) on renal blood flow (RBF) and renin secretion (RS). Studies were conducted in alpha-chloralose-anesthetized dogs maintained on a salt-free diet for at least 3 days. A snare was placed around the left circumflex artery near its origin. The left renal artery and vein were exposed via flank incision, a flow probe was placed around the artery, and a curved needle was inserted into the vein for collection of renal venous blood. Values of blood pressure (BP), RBF, and RS were obtained for a 30-min control period, 4 min after the completion of a 10-ml/kg hemorrhage, 1 and 5 min after CAO, and 15 min after reinfusion. The CAO consisted of two 1-min occlusions separated by a 1-min interval. The results indicate that CAO reflexively inhibits the RS response to nonhypotensive hemorrhage and prevents renal vasoconstriction (P less than 0.05, n = 7). Both effects were completely abolished after vagotomy (n = 5). Renal denervation also abolished the response (n = 5). No response was observed during identical time controls (n = 5). The response was more pronounced in dogs with carotid sinus denervation, even though CAO resulted in marked reductions in BP (20%) under these conditions. These results demonstrate the presence of a cardiorenal reflex that can be activated by myocardial hypoxia and that acutely suppresses RS. This response is more pronounced in the absence of carotid sinus buffering.

Animals↗
PubMed1982

Central and peripheral adrenergic modulation of carotid sinus-induced renin release.

To study central and peripheral mechanisms that regulate the level of circulating renin during activation of the carotid sinus baroreflex, both carotid sinuses were isolated and perfused at constant flow in chloralase-anesthetized dogs. Sinus pressure was controlled by an adjustable reservoir while systemic pressure was stabilized using an external chamber. Arterial renin activity, measured by radioimmunoassay, was increased during sinus hypotension only if systemic pressure was held constant. The renin response was eliminated by either sinus or renal denervation. Administration of propranolol (iv) or phentolamine directly into the renal artery totally blocked the increase in renin during activation of the reflex. Perfusion of a beta-adrenergic blocker (propranolol) or an alpha-adrenergic blocker (phentolamine) through the third and fourth cerebroventricles had no effect on the increase in renin during sinus hypotension, whereas centrally administered clonidine, and alpha-agonist, blocked the response. We conclude that the sinus reflex arc affecting renin release involves not only activation of peripheral alpha- and beta-adrenergic receptors in the kidney but also inhibition of central alpha-adrenergic receptors. No evidence for central beta-involvement was found.

Animals↗
PubMed1981

Characterization of angiotensin pressor responses in the turtle Pseudemys scripta.

Studies were conducted in turtles (Pseudemys scripta) to characterize vascular responses to administration of exogenous angiotensin [Asp1-Ile5]angiotensin II (AII). Marked pressor responses were present following AII administration (2 microgram/kg iv). The pressor response was completely blocked by concomitant administration of an analogue of AII, [Sar1-Ile8]AII. Both alpha-receptor blockade with phenoxybenzamine or catecholamine depletion by reserpine administration reduced the pressor response approximately 50%. Further treatment with [Sar1-Ile8]AII completely blocked the AII pressor response. We conclude that the pressor response to AII in this species that represents an ancient group of reptiles includes a catecholamine-dependent component and direct vascular receptors, both of which are sensitive to AII.

1-Sarcosine-8-Isoleucine Angiotensin II↗