Heart Rate Reflex Responses Research Articles

Paraventricular Nucleus in Acupuncture's Inhibition of the Von Bezold Jarsich Reflex

Electroacupuncture (EA) stimulates specific somatic sensory nerves underlying P5‐6 acupoints and modulates parasympathoexcitatory reflex responses through actions in the brainstem. Although Bezold Jarisch‐induced decreases in blood pressure and heart rate reflex responses are modulated by acupuncture through actions in nucleus tractus solitarius and nucleus ambiguus, the role of the hypothalamus is unclear. The paraventricular nucleus (PVN) regulates sympathetic outflow and blood pressure. Vagal afferent stimulation activates neurons in the PVN but little is known about cardiopulmonary physiological actions in this nucleus. We therefore hypothesized that the PVN participates in the Bezold Jarisch responses and EA modulation of parasympathoexcitatory cardiovascular responses. Rats were anesthetized, ventilated, and heart rate and mean blood pressures were monitored. Application of phenylbiguanide (PBG) every 10 min close to the right atrium induced consistent depressor and bradycardia reflex responses. Unilateral microinjection of kainic acid or kynurenic acid in the PVN reduced the reflex responses. Thirty min of bilateral EA at P5‐6 acupoints reduced the depressor and bradycardia responses lasted for >60 min. Unilateral inhibition of the PVN with 50 nl of naloxone reversed the EA‐inhibition during repeated PBG‐induced responses. EA‐related c‐Fos PVN neurons were juxtaposed to endorphinergic PVN fibers. Thus, cardiopulmonary PVN responses are important in processing acupuncture modulation of cardiovascular inhibitory reflexes.Funded by HL‐63313, HL‐72125.

Central and peripheral mechanisms underlying gastric distention inhibitory reflex responses in hypercapnic-acidotic rats.

We have observed that in chloralose-anesthetized animals, gastric distension (GD) typically increases blood pressure (BP) under normoxic normocapnic conditions. However, we recently noted repeatable decreases in BP and heart rate (HR) in hypercapnic-acidotic rats in response to GD. The neural pathways, central processing, and autonomic effector mechanisms involved in this cardiovascular reflex response are unknown. We hypothesized that GD-induced decrease in BP and HR reflex responses are mediated during both withdrawal of sympathetic tone and increased parasympathetic activity, involving the rostral (rVLM) and caudal ventrolateral medulla (cVLM) and the nucleus ambiguus (NA). Rats anesthetized with ketamine and xylazine or α-chloralose were ventilated and monitored for HR and BP changes. The extent of cardiovascular inhibition was related to the extent of hypercapnia and acidosis. Repeated GD with both anesthetics induced consistent falls in BP and HR. The hemodynamic inhibitory response was reduced after blockade of the celiac ganglia or the intraabdominal vagal nerves with lidocaine, suggesting that the decreased BP and HR responses were mediated by both sympathetic and parasympathetic afferents. Blockade of the NA decreased the bradycardia response. Microinjection of kainic acid into the cVLM reduced the inhibitory BP response, whereas depolarization blockade of the rVLM decreased both BP and HR inhibitory responses. Blockade of GABA(A) receptors in the rVLM also reduced the BP and HR reflex responses. Atropine methyl bromide completely blocked the reflex bradycardia, and atenolol blocked the negative chronotropic response. Finally, α(1)-adrenergic blockade with prazosin reversed the depressor. Thus, in the setting of hypercapnic-acidosis, a sympathoinhibitory cardiovascular response is mediated, in part, by splanchnic nerves and is processed through the rVLM and cVLM. Additionally, a vagal excitatory reflex, which involves the NA, facilitates the GD-induced decreases in BP and HR responses. Efferent chronotropic responses involve both increased parasympathetic and reduced sympathetic activity, whereas the decrease in BP is mediated by reduced α-adrenergic tone.

Transmission of arterial baroreflex signals depends on neuronal nitric oxide synthase.

Because inhibition of neuronal nitric oxide synthase in the nucleus tractus solitarii blocks cardiovascular responses to activation of local glutamate receptors, and because glutamate is a neurotransmitter of baroreceptor afferent nerves, we sought to test the hypothesis that neuronal nitric oxide synthase inhibition would block baroreflex transmission and cause hypertension. We determined reflex heart rate responses to intravenous phenylephrine and sodium nitroprusside in 5 anesthetized rats before and after bilateral microinjection (100 nL) of the neuronal nitric oxide synthase inhibitor AR-R 17477 (7.5 nmol) into the nucleus tractus solitarii. The inhibitor significantly increased mean arterial pressure without affecting heart rate, and it significantly reduced the gain of the baroreflex. After administration of the inhibitor, reflex responses of heart rate to changes in mean arterial pressure were always less than those responses to the same, or less, change in mean arterial pressure in the same animal without administration of the inhibitor. Microinjection of saline (100 nL) bilaterally into the nucleus tractus solitarii did not lead to hypertension or change baroreflex responses. These data support the hypothesis and suggest that neuronal nitric oxide synthase is critical to transmission of baroreflex signals through the nucleus tractus solitarii.

DAILY EXERCISE ATTENUATED THE SYMPATHETIC COMPONENT OF THE SPONTANEOUS ARTERIAL BAROREFLEX CONTROL OF HEART RATE IN HYPERTENSIVE RATS

The influence of daily spontaneous running on the sympathetic and parasympathetic components of the spontaneous arterial baroreflex control of heart rate was examined in 22 female spontaneously hypertensive rats [12 sedentary and 10 daily spontaneous running]. Following 8 weeks of sedentary control or daily spontaneous running, animals were chronically instrumented with an arterial catheter. Daily spontaneous running resulted in an increased heart weight/body weight ratio (5.2±0.27 vs 4.3±0.01 g/kg) and a resting bradycardia (321±8 bpm vs 360±6). The spontaneous changes in arterial pressure and the reflex responses of heart rate were examined under three experimental conditions: 1) pre-blockade, 2) following β1-adrenergic receptor blockade, and 3) following muscarinic-cholinergic receptor blockade. Daily spontaneous running attenuated the spontaneous gain of the arterial baroreflex control of heart rate (56%). After muscarinic-cholinergic receptor blockade, the spontaneous gain remained reduced in daily spontaneous running rats (57%). In contrast, after β1-adrenergic receptor blockade the spontaneous gain was not different between sedentary control and daily spontaneous running animals. Results demonstrate that daily spontaneous running decreased the sympathetic component resulting in an apparently greater influence of the parasympathetic component on the spontaneous arterial baroreflex control of heart rate.

The effects of morphine on supraspinal and propriospinal somatocardiac reflexes in anesthetized rats

In anesthetized rats, the effects of i.v. injection of morphine on supraspinally- and spinally-mediated tachycardiac reflex responses of heart rate (HR) and cardiac sympathetic nerve reflex activity were examined following electrical stimulation of either a non-segmental hindlimb (tibial) or a segmental (3rd or 4th intercostal, IC3–4) afferent nerve. In central nervous system (CNS)-intact rats, the supraspinally-mediated reflex increase in HR in response to tibial afferent nerve stimulation was augmented by morphine, whereas the increase in response to IC3–4 afferent nerve stimulation was variable. Both the supraspinally-mediated myelinated (A) and unmyelinated (C) reflex discharges in the cardiac sympathetic nerve elicited by tibial afferent nerve stimulation were augmented by morphine. The effects of morphine on A- and C-sympathetic reflex discharges elicited by IC3–4 afferent nerve stimulation varied depending upon whether the discharge was of supraspinal or spinal origin. In spinal rats (spinalized at the cervical level), tibial afferent nerve stimulation did not produce any HR response, whereas IC3–4 afferent nerve stimulation produced a reflex increase in both HR and sympathetic reflex discharges of spinal origin. Furthermore, these spinal HR and sympathetic nerve reflex responses were inhibited by morphine. In conclusion, morphine depressed somatocardiac sympathetic reflexes at the spinal level, but enhanced these reflexes at the supraspinal level, leading to different effects of morphine on somatically-induced HR responses of supraspinal and spinal origins depending upon the segmental levels of afferent nerves stimulated.

Arterial baroreflex resetting mediates postexercise reductions in arterial pressure and heart rate.

We tested the hypothesis that postexercise reductions in arterial pressure and heart rate (HR) are mediated by a lowering of the operating point and a reduction in the gain of the arterial baroreflex. To test this hypothesis, spontaneous changes in arterial pressure and the reflex responses of HR were examined before and after a single bout of mild to moderate dynamic exercise in 19 spontaneously hypertensive rats (SHR, 10 male and 9 female). Eleven SHR subjected to sinoaortic denervation (SAD) (6 male, 5 female) were also studied. All rats were instrumented with an arterial catheter for the measurement of arterial pressure and HR. After exercise, arterial pressure and HR were reduced below preexercise levels. Furthermore, the operating point and spontaneous gain (G) of the arterial baroreflex were reduced. Specifically, after exercise, the spontaneous range of HR (P1, 50%), the pressure at the midpoint of the pressure range (P3, 13%) and the HR at the midpoint of the HR range (H3, 10%), the spontaneous minimum HR (P4, 8%) and maximum HR (10%), and G (76%) were significantly attenuated. SAD significantly attenuated the relationship between arterial pressure and HR by reducing G (males 94%, females 95%). These results demonstrate that acute exercise resulted in a postexercise resetting of the operating point and a reduction in the gain of the arterial baroreflex. Furthermore, these data suggest that postexercise reductions in arterial pressure and HR are mediated by a lowering of the operating point of the arterial baroreflex.

ANP enhances bradycardic reflexes in normotensive but not spontaneously hypertensive rats.

Baroreflex control of heart rate in spontaneously hypertensive rats (SHR) is defective, largely because of a poor vagal contribution to the reflex. We have demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex bradycardia in normotensive rats through an action on nonarterial vagal afferent pathways. In the present study, we investigated whether ANP could reverse the baroreflex abnormality in SHR. Heart rate reflexes were activated by three different methods in conscious, instrumented SHR and Wistar-Kyoto rats (WKY) in the presence of intravenous infusions of vehicle (saline) or rat ANP (150 ng/kg per minute). Heart rate responses were measured by (1) the steady-state changes in blood pressure after alternating slow infusions (over approximately 15 to 30 seconds) of a pressor (methoxamine) and depressor (nitroprusside) drug (stimulating predominantly arterial baroreceptors), (2) the ramp method of rapid infusion of methoxamine (over < 10 seconds; stimulating arterial and cardiopulmonary baroreceptors), and (3) the von Bezold-Jarisch method of activating chemically sensitive cardiac receptors through serotonin injections. ANP enhanced the heart rate range of the arterial baroreflex (steady-state method) by 13 +/- 3% in WKY but had no significant effect on the sensitivity or any other parameter of the steady-state baroreflex. When a very rapid rise in blood pressure was elicited by the ramp method in WKY, ANP significantly enhanced baroreflex bradycardia (sensitivity increased by 29 +/- 9%, P < .05). ANP also enhanced the bradycardia of the von Bezold-Jarisch reflex (by 33 +/- 16%, P < .05) in WKY. By contrast, ANP did not influence baroreceptor or chemoreceptor heart rate reflex responses in SHR. We conclude that in normotensive rats, ANP facilitates cardiopulmonary bradycardic reflexes. The lack of effect of ANP in SHR may be related to an underlying structural or genetic alteration in their cardiac sensors, perhaps associated with cardiac hypertrophy, that prevents the ANP-induced activation of cardiac sensory afferents, resulting in cardioinhibition.

Impaired baroreflex control of heart rate in high-renin renal hypertension.

The reflex responses of heart rate (HR) to bolus injection and infusion of phenylephrine and nitroglycerine were studied in rats with one-kidney, one clip (1-K, 1C) hypertension and hypertension produced by aortic ligation. Rats with mild 1-K, 1C hypertension (147 +/- 4 mmHg) and a normal renin-angiotensin system (RAS) activity had normal bradycardic and tachycardic responses, whereas rats with severe hypertension (208 +/- 3 mmHg) and over-active RAS showed impairment (70-80%) of the responses. After 12 days of aortic ligation rats with mild (146 +/- 2 mmHg) and severe (175 +/- 3 mmHg) hypertension exhibited overactivity of the RAS and marked impairment of the baroreflex control of HR. Normalization of RAS activity in rats with mild hypertension 60 days after aortic ligation, coincided with normalization of the bradycardic responses, whereas the abnormality persisted in those rats with severe hypertension in which hyperactivity of RAS also persisted. The response to 20-s carotid occlusion and the HR responses to electrical stimulation of the vagus nerve were normal in rats with renal hypertension, 12 days after aortic ligation. An ether inhalation test produced a marked reduction of 60% in the HR of control awake rats accompanied by a 46 +/- 5 mmHg increase in blood pressure. Reflex pathways other than those through the baroreceptors were largely responsible for the bradycardia since responses remained unchanged in rats with sino-aortic denervation (SAD) or when the pressure increase was prevented by phenoxybenzamine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate reflex responses during gestation in normotensive and spontaneously hypertensive rats following angiotensin II and vasopressin.

Gestation in the human and in rats is accompanied by a decrease in blood pressure and a reduction of the pressor response to vasoconstrictor agents. In humans, the decreased vascular reactivity to angiotensin II (AII) may occur simultaneously with a state of increased baroreceptor sensitivity. We have consequently evaluated the heart rate response to elevation of blood pressure following administration of either AII or arginine8-vasopressin (AVP) in conscious unrestrained, nonpregnant, or term-pregnant normotensive rats (Sprague-Dawley, SDR; Wistar-Kyoto, WKR) and in spontaneously hypertensive rats (SHR). The decrease in heart rate in response to increase in blood pressure by AII in nonpregnant animals was similar in SDR and SHR, but much greater in WKR. The heart rate response to increase in blood pressure by AVP was similar in all three strains of cycling rats. Gestation (20th day) did not change the heart rate response to increase in blood pressure by AII in normotensive animals, but increased slightly the reflex responses in SHR, as shown by a significant increase of the slope of the relationship of the decrement in heart rate versus the increment of blood pressure. The heart rate response to increase in blood pressure by AVP was greater during gestation in normotensive SDR and WKR, but not in SHR. These results show that the heart rate responses to an increase in blood pressure by vasoconstrictor peptides is dependent on the strain of animals used and suggest that the baroreceptor reflexes play a minor role in the blunted effect of vasconstrictor agens at the end of gestation in normotensive and spontaneously hypertensive rats.

Rabbit carotid baroreflexes after carotid sympathectomy, vagotomy, and beta blockade.

Factors that modify carotid vascular baroreflexes were studied in anesthetized rabbits after section of the cervical aortic nerves. We recorded steady-state reflex responses of heart rate (HR) and mean arterial pressure (MAP) to changes in isolated nonpulsatile carotid intrasinus pressures (ISP) over a wide range. These measurements and the procedures were repeated 1) after sympathetic denervation of the carotid sinuses by section of the cervical sympathetic nerve below the superior cervical ganglia; 2) after cervical vagotomy; and 3) after beta-receptor blockade by propranolol administration. The linearity of the MAP-ISP relation curve slope was determined between ISP levels of 63 and 100 mmHg. Comparison of results before and after sympathetic denervation of the sinuses indicated that the denervation significantly lowered the position of the MAP-ISP relation curve over a mid-ISP range. Subsequent vagotomy significantly elevated both HR-ISP relation curve and MAP-ISP relation curve. AFter beta-receptor blockade HR remained constant, whereas the slope of the MAP-ISP relation curve decreased to -1.34 from the slope of -2.26 before blockade. Comparison of results before and after beta blockade in the vagotomized animals suggested a substantial cardiac influence on carotid reflex control of MAP.