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M M Knuepfer

Publications and source records attributed to M M Knuepfer.

54 records · Page 3Linked to original sources
PubMed1990

Hemodynamic and sympathetic effects of spinal administration of neuropeptide Y in rats.

Intrathecal administration of 4 nmol/kg neuropeptide Y in Dial-urethane-anesthetized rats elicited decreases in arterial pressure, renal sympathetic nerve activity, and a slight decrease in heart rate. The depressor response was associated with a sustained hindquarters and mesenteric vasodilation resulting in a decrease in total peripheral resistance. Intrathecal NPY also resulted in a decrease in renal sympathetic nerve activity. There was a positive correlation between the percent changes in arterial pressure and renal sympathetic nerve activity. With the use of renal nerve activity and heart rate as indexes, NPY resulted in a decrease in baroreflex sensitivity. The depressor effect of intrathecal NPY did not appear to be due to spinal vasoconstriction and ischemia, since spinal microvascular resistance was decreased slightly. We conclude that the intrathecal administration of NPY produces an inhibition of sympathetic nerve activity, resulting in a decrease in total peripheral resistance and arterial pressure.

Animals↗
PubMed1989

Effects of endothelin on regional hemodynamics in conscious rats.

Endothelin is a potent vasoactive peptide in anesthetized rats and isolated vascular smooth muscle. This study was performed to describe the hemodynamic effects of endothelin in conscious, freely moving rats. Endothelin (0.067-2 nmol/kg i.v.) produced long-lasting, dose-dependent increases in arterial pressure, mesenteric and, to a lesser degree, hindquarters vascular resistances and decreases in heart rate. We suggest that endothelin may play an important role in regulation of arterial pressure by modulating peripheral vasomotor tone.

Animals↗
PubMed1989

Mechanism of pressor response to posterior hypothalamic injection of neuropeptide Y.

Unilateral microinjection of neuropeptide Y (NPY) into the posterior hypothalamic nucleus was previously found to evoke an increase in mean arterial pressure (MAP) in urethan-anesthetized rats. In this study, the mechanism by which this increase occurs was examined. Pretreatment of rats with 2.0 mg/kg (iv) of phenoxybenzamine, or 7.5 mg/kg (iv) of pentolinium, resulted in a significant reduction in the peak MAP evoked by microinjection of NPY (2.35 nmol) into the posterior hypothalamic nucleus. Administration of the vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)]AVP (10 micrograms/kg iv) before microinjection of NPY failed to attenuate the increase in MAP. Similar results were obtained with respect to the effect of these three antagonists on the increase in MAP evoked by injection of the cholinergic muscarinic agonist carbachol (5.48 nmol) into the posterior hypothalamic nucleus. Furthermore, microinjection of NPY or carbachol elicited a significant elevation of renal sympathetic nerve activity and an increase in resistance of the hindquarter vascular bed. However, NPY elicited a decrease and carbachol an increase in the resistance of the mesenteric bed, whereas NPY elicited an increase and carbachol a decrease in the resistance of the renal bed. These results suggest that NPY elicits an increase in MAP via centrally mediated sympathetic excitation. Furthermore, NPY and carbachol differentially affect sympathetic outflow to peripheral vascular beds after microinjection into the posterior hypothalamic nucleus.

Animals↗
PubMed1989

Regional hemodynamic and baroreflex effects of endothelin in rats.

Endothelin is a peptide with potent, long-lasting pressor effects characterized by increases in mesenteric and hindquarters vascular resistance and bradycardia following an initial, transient depressor response. This study examined the mechanisms of action of endothelin on regional hemodynamics in conscious, freely moving rats and on baroreflex sensitivity both in conscious and chloralose-anesthetized rats. The pressor response to endothelin (0.67 nmol/kg) was attenuated by nifedipine (25 micrograms/kg) and augmented by chloralose anesthesia. The bradycardia was attenuated by pentolinium (10 mg/kg), atropine methyl sulfate (0.5 mg/kg), or chloralose anesthesia. Hindquarter vaso-constriction was attenuated by nifedipine, pentolinium, and atropine, whereas mesenteric vasoconstriction was less sensitive to blockade. The vasopressin V1 antagonist, [d(CH2)5Tyr(Me)]-AVP (20 micrograms/kg), indomethacin (5 mg/kg), or verapamil (150 micrograms/kg) did not affect any of these cardiovascular responses. Renal sympathetic nerve activity was reduced similarly in chloralose-anesthetized rats to pressor responses elicited by either phenylephrine or endothelin, and the slope of the baro-reflex function curve after endothelin was similar to that of phenylephrine. These results suggest that endothelin is a potent vasoconstrictor in which its action on visceral and skeletal muscle vasculature is mediated by somewhat different mechanisms. Endothelin does not alter baroreceptor reflex control of sympathetic nerve activity or heart rate.

Animals↗
PubMed1988

Spinal projections of renal afferent nerves in the rat.

This study was designed to describe renal afferent information with respect to its intraspinal projections, convergence with cutaneous inputs, ascending projections, and modulation by descending fiber tracts. Extracellular recordings were made from neurons in the spinal gray while electrically stimulating the renal nerves in chloralose-anesthetized, artificially ventilated rats. Almost all neurons (n = 119) were spontaneously active. Some responses consisted of high-frequency bursts while others consisted of fewer than 6 action potentials. Response onset latencies to renal nerve stimulation were consistent with activation by thinly myelinated or unmyelinated afferents. Several neurons in deeper laminae were inhibited by stimulation of renal afferents. Most neurons were located in laminae IV and V. Some were located in laminae I, VII and VIII. All neurons were located at spinal levels T10 to L1. Most neurons responded to both noxious and non-noxious mechanical cutaneous stimuli from relatively large receptive fields on the ipsilateral flank. Response latencies to cutaneous electrical stimulation were shorter than those to renal nerve stimulation. Neurons in intact and spinally transected rats responded with similar onset latencies and durations to renal nerve stimulation. However, neurons in spinally transected rats exhibited prolonged responses to cutaneous stimulation. Axons of 25% of the neurons projected through the cervical spinal cord in the ventrolateral funiculus. They had conduction velocities of 12-32 m/s. These data provide the first electrophysiological description of spinal projections of renal afferent fibers in the rat.

Afferent Pathways↗
PubMed1987

The conduction velocities and spinal projections of single renal afferent fibers in the rat.

This study was designed to examine the conduction velocities and spinal projections of renal afferent fibers in the rat using electrophysiological techniques. In chloralose-anesthetized rats, we electrically stimulated the peripheral ends of cut, lower thoracic and upper lumbar dorsal roots and recorded and averaged antidromically conducted action potentials in the renal nerves. Of 284 single axons responding to stimulation of ipsilateral dorsal roots T9-L1, the majority were activated by stimulating roots T11-T13. No antidromic responses could be elicited by stimulating the contralateral dorsal roots. Afferent fibers were divisible into two groups, distinguished by their conduction velocities: a population of slowly conducting axons, presumably composed of both unmyelinated (0.3-2 m/s, 76%) and thinly myelinated (2-9 m/s, 19%) fibers, and a population of more rapidly conducting, small myelinated axons (12-32 m/s, 5%). Slowly and more rapidly conducting fibers were not differentially distributed among dorsal roots. Postexperimental histological examination of nerves revealed small myelinated axons with diameters appropriate for some, but not for all, of the axons with conduction velocities in the myelinated range. These results indicate that single myelinated and unmyelinated primary afferent axons can be identified by antidromic stimulation in autonomic nerves of rat. They provide the first electrophysiological description of afferent renal nerve fibers in the rat, and they verify the predominantly unmyelinated nature of these fibers.

Afferent Pathways↗
PubMed1987

Sensory input to single neurons in the amygdala of the cat.

We determined functionally the afferent projections from exteroceptors and enteroceptors (visceral receptors) to single cells of the amygdala. Recordings were made in chloralosed cats from 249 cells in four subnuclei of the amygdala. Forty-six percent of cells tested responded to carotid sinus nerve stimulation and more than one-half of them responded to selective baroreceptor or chemoreceptor activation or to electrical stimulation of the locus ceruleus. Of 11 cells responding similarly (inhibition) to carotid sinus nerve stimulation and to selective baroreceptor activation, all were inhibited by locus ceruleus stimulation, also. Approximately 17% of cells tested responded to at least one exteroceptive stimulus (acoustic, optic, or tactile) whereas 14% responded to more than one exteroceptive stimulus in a similar manner. Amygdalar cells were also identified that responded to visceral (renal nerve) and somatic (iliac nerve) stimulation. Many cells received input both from enteroreceptors and from exteroceptors. These results suggest that baroreceptor input to single neurons in the amygdala is often convergent with input from the locus ceruleus. In addition, the convergence of both internal and external sensory inputs to single neurons is further evidence that the amygdala is a site for the integration of responses to arousal.

Acoustic Stimulation↗
PubMed1986

Baroreceptor sensitivity during desynchronized sleep.

Sleep is characterized by periods of cortical and subcortical desynchronization similar to that observed during arousal. Because baroreflex control of heart rate is suppressed in the aroused state, the present study compared the cardiac index of baroreflex sensitivity in awake cats with that during desynchronized sleep to determine the level of arousal and its affect on autonomic regulation. Cats were prepared for long-term arterial pressure, cortical, and subcortical EEG and EMG recording. After acclimatization to the laboratory, cats engaged in spontaneous periods of desynchronized sleep. During this period, a bolus of angiotensin II was injected i.v. and the subsequent change in the R-R interval of the cardiac cycle was recorded during the rising phase of the pressor response. These values were compared with values obtained from the same cats during quiet and active wakefulness and those obtained during drug-induced desynchronized sleep with gamma-hydroxybutyrate. The values obtained during naturally occurring desynchronized sleep were comparable to those observed during drug-induced desynchronized sleep. In contrast, the increase in the R-R interval in awake cats, particularly quiet ones, was greater than that seen during desynchronized sleep or during active periods in the awake animal. These data suggest that there is a correlation between the level of arousal, as measured by EEG activity, and the cardiomotor component of baroreflexes.

Animals↗
PubMed1986

Effect of afferent renal nerve stimulation on blood pressure, heart rate and noradrenergic activity in conscious rats.

The effects of electrical stimulation of afferent renal nerves on arterial pressure, heart rate, and alpha-methyltyrosine-induced disappearance of norepinephrine in the hypothalamus, contralateral kidney, intestine, and skeletal muscle were studied in conscious rats. There was a significant increase in arterial pressure in response to afferent renal nerve stimulation. There was no significant change in the turnover of norepinephrine in the hypothalamus. However, there was a significant increase in the turnover of norepinephrine in the skeletal muscle, a tendency toward an increase in the intestine, and no change in the contralateral kidney. These results indicate that activation of afferent renal nerve fibers does not change noradrenergic activity in the hypothalamus yet produces a differential sympathetic outflow. Secondly, the increased turnover of norepinephrine in skeletal muscle may be contributing to the increase in arterial pressure.

Animals↗
PubMed1985

Effects of baroreceptor activation on single unit activity of the anteroventral third ventricle region of the rat.

The anteroventral third ventricular (AV3V) region, part of the preoptic area, is involved in neurohumoral regulation of the cardiovascular system and in the development of experimental hypertension. Single unit activity within the AV3V region of the rat was recorded in response to the activation of arterial baroreceptors produced by intravenous phenylephrine or by aortic occlusion. Both inhibition and excitation of units was observed in response to an increase in arterial pressure with the highest incidence of responses in the median and periventricular subnuclei of the preoptic area. These data provide functional evidence for the neural projections from medullary baroreceptor fiber terminations to the AV3V region and preoptic area.

Animals↗
PubMed1985

An anomalous vagorenal reflex pathway in the cat.

Although physiological investigations support the view that the innervation to the kidney is primarily sympathetic in origin, there is anatomic evidence suggesting direct vagal projections to the kidney. We examined electrophysiologically the possibility that neural connections exist between the cervical vagus and renal nerves. Electrical stimulation of the peripheral segment of the cut cervical vagus evoked electrical activity in the central segment of cut renal nerve of chloralose-anesthetized, paralyzed cats. The evoked potentials (vagorenal responses) displayed components with peak latencies of about 50, 120, and 500 ms. Another peak at about 175 ms was also seen in some cases. In addition, a period of postexcitatory depression occurred between approximately 180 and 400 ms after delivery of the stimulus. Evoked responses were recorded in the contralateral as well as the ipsilateral renal nerves. In contrast, stimulation of the central cut end of renal nerves did not elicit responses in the cervical vagus. Vagorenal responses were not altered by cutting the subdiaphragmatic vagus indicating that the abdominal vagus was not involved in this response. Electrical activity in renal nerves elicited by vagal stimulation could be eliminated by either ganglionic blockade or by cutting or cooling the splanchnic nerves. Finally, supraspinal ischemia abolished the vagorenal response. These data suggest that a vagorenal reflex pathway exists and that the potentials recorded in renal nerves are due to activation of aberrant sensory fibers traveling from the peripheral segment of the cut cervical vagus to the central nervous system, where they excite a sympathetic efferent pathway to the kidney.

Animals↗
PubMed1985

Properties of renobulbar afferent fibers in rats.

Myelinated renobulbar sensory fibers project directly from the kidney to the dorsomedial medulla. They can be activated by punctate stimulation of the kidney. In these experiments we studied the physiological modality and the intrarenal locations of the receptors for renobulbar fibers. Renobulbar fibers were identified in recordings from the renal nerves of anesthetized rats. Although nonmyelinated renal afferent fibers were activated by increased intrarenal pressure and by chemical stimuli, no renobulbar fiber activated by punctate mechanical stimulation was activated by these other stimuli. Occasionally single fibers could be activated by punctate stimulation of two or more sites on the surface of the kidney, and responses from each site could be selectively blocked with a local anesthetic. Renobulbar fibers could be activated by electrical stimulation of discrete regions deep within the renal parenchyma. Increased intrarenal pressure increased the sensitivity of receptors to punctate stimulation but not to electrical stimulation of the kidney. We conclude that myelinated renal afferent fibers in the rat respond to external mechanical stimuli, lie deep within the renal parenchyma, and occasionally have more than one receptor.

Afferent Pathways↗
PubMed1984

Identification of brainstem projections mediating hemodynamic responses to stimulation of the anteroventral third ventricle (AV3V) region.

The anteroventral third ventricle (AV3V) region is necessary for the development of several models of experimental hypertension in rats. Electrical stimulation of the AV3V region produces hindlimb vasodilation, mesenteric and renal vasoconstriction and bradycardia resulting in a depressor response. The effect of selective ablation of diencephalic and mesencephalic sites upon responses to AV3V stimulation was employed earlier to functionally identify descending tracts from the AV3V region through the ventromedial hypothalamus and rostral central gray. This study was performed in a similar manner to identify more caudal projections from the AV3V region to the level of pons and medulla. The vasodilator response to AV3V stimulation was dependent upon sites in and around the nucleus tractus solitarius, although the region receiving primary baroreceptor afferent input was not part of this projection. Visceral vasoconstrictor tracts were less clearly defined suggesting that these projections traverse diffusely through the ventrolateral tegmentum. These data suggest that a topographical differentiation of descending vasomotor tracts from the AV3V region exists in the brainstem of the rat.

Animals↗
PubMed1984

Vasomotor projections from the anteroventral third ventricle (AV3V) region.

The anteroventral third ventricle (AV3V) region is necessary for the development of a variety of models of experimental hypertension. Neuroanatomic studies have identified descending projections from this region to the mesencephalic central gray and tegmentum. This study was done to identify functionally the projections involved in cardiovascular regulation from the AV3V region to the mesencephalon. Regional hemodynamic responses to electrical stimulation of the AV3V region were compared with responses to stimulation of the rostral central gray, and these responses were compared before and after ablation of mesencephalic tissue. Stimulation of the AV3V region elicited hindquarter, vasodilation and renal and mesenteric vasoconstriction associated with a depressor response and bradycardia. These responses were partially dependent on adrenal catecholamines since adrenalectomy reduced hindquarter, mesenteric, and depressor responses. Regional hemodynamic responses to central gray stimulation were qualitatively similar and also demonstrated a partial dependence on adrenal catecholamines. After electrolyte ablation of central gray tissue, significant reductions in hindquarter, mesenteric, and depressor responses to AV3V stimulation were observed. These observations suggest that a cardiovascular control system important for the development of several models of hypertension may be dependent on neuronal projections from the rostral medial hypothalamus through the mesencephalic central gray.

Adrenal Glands↗
PubMed1984

Effect of subfornical organ ablation on the development of renal hypertension.

Both the AV3V and the SFO have been shown to mediate dipsogenic and pressor responses to angiotensin. Neuroanatomical projections from the SFO to structures in the AV3V region have been associated with angiotensin effects. Since it has been shown that ablation of the AV3V region attenuates the development of experimental renal hypertension in rats, the effect of ablation of the SFO on the development of renal hypertension was examined. One kidney renal hypertension was produced by placing a figure of eight silk wrap around one kidney and removing the contralateral kidney. Rats with SFO lesions developed hypertension to a similar extent as rats with a sham lesion procedure. This study demonstrates that unlike the AV3V region the SFO is not critical for the development of non-renin dependent renal hypertension.

Animals↗
PubMed1981

Capsaicin treatment in adult Wistar-Kyoto and spontaneously hypertensive rats: effects on nociceptive behavior and cardiovascular regulation.

Effects of s.c. capsaicin pretreatment on nociception, mean systemic arterial blood pressure, and dose-response curves for depressor effects of substance P (SP) and pressor effects of angiotension II (AII) and norepinephrine (NE) were examined in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Capsaicin pretreatment significantly elevated hot plate and tail flick latencies in SHR subjects but was without effect in WKY rats. Capsaicin pretreatment significantly reduced mean systemic arterial blood pressure in rats of both strains. Both vehicle- and capsaicin-treated WKY subjects exhibited greater depressor responses than did subjects of the corresponding SHR groups after i.v. SP administration. Vehicle-treated SHR subjects exhibited greater pressor responses to both AII and NE than did rats of the vehicle-treated WKY group. Capsaicin treatment decreased the sensitivity of WKY rats to the pressor effects of both AII and NE. Strain differences involving nociception, cardiovascular regulation, and responses to capsaicin may underly the results reported.

Angiotensin II↗
PubMed1979

Vasodilator response to histamine: dependence upon the site of administration.

Histamine causes vasodilation in part by interacting with histamine H2 receptors. The present study was undertaken to evaluate the difference in vasodilator sensitivity of H2 receptors on the inside compared to the outside of the vessel. In order to induce tone, norepinephrine was administered to an in vitro preparation of rabbit ear artery treated with mepyramine to block H1 receptors. Histamine was then either selectively perfused through the artery or added to the outside of the vessel via the organ bath. The outside of the artery was found to be twice as sensitive to the vasodilator effect of histamine as the inside. These data provide the first evidence for greater extraluminal sensitivity of vascular smooth muscle and suggest that the response to histamine will depend in part on the route the amine takes to reach receptors, e.g., from blood-borne sources or from extraluminal stores.

Animals↗