Impact of l-NAME on the cardiopulmonary reflex in cardiac hypertrophy

There is evidence that in cardiac failure, there is defective baroreceptor reflex control of sympathetic nerve activity. Often, cardiac failure is preceded by a state of cardiac hypertrophy in which there may be enhanced performance of the heart. This study investigated whether in two different models of cardiac hypertrophy, there was an increased contribution of nitric oxide (NO) to the low-pressure baroreceptor regulation of renal sympathetic nerve activity (RSNA) and nerve-dependent excretory function. Administration of a volume load, 0.25* body wt/min saline for 30 min, in normal rats decreased RSNA by 40* and increased urine flow by some 9-fold. Following nitro-l-arginine methyl ester (l-NAME) administration, 10 μg·kg−1·min−1 for 60 min, which had no effect on blood pressure, heart rate, or RSNA, the volume load-induced renal sympathoinhibitory and excretory responses were markedly enhanced. In cardiac hypertrophy states induced by 2 wk of isoprenaline/caffeine or 1 wk thyroxine administration, the volume challenge failed to suppress RSNA, and there were blunted increases in urine flow in the innervated kidneys, but following l-NAME infusion, the volume load decreased RSNA by 30–40* and increased urine flow by some 20-fold in the innervated kidneys, roughly to the same extent as observed in normal rats. These findings suggest that the blunted renal sympathoinhibition and nerve-dependent diuresis to the volume load in cardiac hypertrophy are related to a heightened production or activity of NO within either the afferent or central arms of the reflex.

Baroreflex control of heart rate by oxytocin in the solitary-vagal complex

Previous work demonstrated that oxytocinergic projections to the solitary vagal complex are involved in the restraint of exercise-induced tachycardia (2). In the present study, we tested the idea that oxytocin (OT) terminals in the solitary vagal complex [nucleus of the solitary tract (NTS)/dorsal motor nucleus of the vagus (DMV)] are involved in baroreceptor reflex control of heart rate (HR). Studies were conducted in male rats instrumented for chronic cardiovascular monitoring with a cannula in the NTS/DMV for brain injections. Basal mean arterial pressure and HR and reflex HR responses during loading and unloading of the baroreceptors (phenylephrine/sodium nitroprusside intravenously) were recorded after administration of a selective OT antagonist (OTant) or OT into the NTS/DMV. The NTS/DMV was selected for study because this region contains such a specific and dense concentration of OT-immunoreactive terminals. Vehicle injections served as a control. OT and OTant changed baroreflex control of HR in opposite directions. OT (20 pmol) increased the maximal bradycardic response (from −56 ± 9 to −75 ± 11 beats/min), whereas receptor blockade decreased the bradycardia (from −61 ± 13 to −35 ± 2 beats/min). OTant also reduced the operating range of the reflex, thus decreasing baroreflex gain (from −5.68 ± 1.62 to −2.83 ± 1.05 beats · min−1 · mmHg−1). OT injected into the NTS/DMV of atenolol-treated rats still potentiated the bradycardic responses to pressor challenges, whereas OT injections had no effect in atropine-treated rats. The brain stem effect was specific because neither vehicle administration nor injection of OT or OTant into the fourth cerebral ventricle had any effect. Our data suggest that OT terminals in the solitary vagal complex modulate reflex control of the heart, acting to facilitate vagal outflow and the slowdown of the heart.

Glucocorticoids modulate baroreflex control of heart rate in conscious normotensive rats

The effect of glucocorticoids on arterial baroreceptor reflex control of heart rate (HR) was determined in conscious rats. Corticosterone (Cort) treatment for 4–6 days doubled plasma Cort in Cort-treated relative to control rats. Cort had no significant effect on mean arterial pressure (MAP) or HR. Ramped changes in MAP were produced using infusions of phenylephrine and nitroprusside. Baroreflex control of HR was analyzed using a four-parameter logistic function. The midpoint of the baseline baroreflex function curve was significantly increased in Cort-treated ( n = 14) relative to control ( n = 14) rats (112 ± 2 vs. 98 ± 2 mmHg, n = 14), and the slope was significantly decreased (0.065 ± 0.002 vs. 0.091 ± 0.007). Three hours after the glucocorticoid type II receptor antagonist mifepristone (Mif) was administered to Cort-treated rats ( n = 8), the midpoint of the baroreflex function was significantly reduced from 113 ± 4 to 99 ± 2 mmHg, and the slope was significantly increased from 0.061 ± 0.004 to 0.083 ± 0.005. Mif decreased HR in Cort-treated rats from 355 ± 17 to 330 ± 14 beats/min ( P = 0.04) but did not alter MAP (111 ± 2 to 107 ± 3 mmHg, P = 0.14). Mif had no significant effects on baroreflex function in control rats. Therefore, a moderate elevation in Cort for several days causes pressure-independent modulation of baroreflex control of HR.

Effects on sympathetic activity of 8-OHDPAT and clonidine in cat medullary lateral tegmental field

This study was designed to test the hypothesis that 8-hydroxy-2-(di- n-propylamino)tetralin (8-OHDPAT) and clonidine reduce sympathetic nerve discharge (SND) and mean arterial pressure (MAP), in part by actions in the medullary lateral tegmental field (LTF). We microinjected these drugs bilaterally into the LTF of baroreceptor-innervated and -denervated cats anesthetized with Dial-urethane. Neither drug altered SND (as quantified by using power spectral analysis) or MAP when injected into the LTF of baroreceptor-denervated cats. However, cardiac-related power in SND was significantly increased to 148 ± 12 (mean ± SE) and 149 ± 5% of control by microinjections of 8-OHDPAT ( n = 5) and clonidine ( n = 5), respectively, in baroreceptor-innervated cats whose MAP was kept constant; there was no change in 0- to 6-Hz power or total power. SND was significantly reduced by microinjection of these drugs into the rostral ventrolateral medulla of baroreceptor-innervated and -denervated cats. In conclusion, although 8-OHDPAT and clonidine did not reduce SND when injected into the LTF, they acted in this region to facilitate baroreceptor reflex control of SND, as evidenced by a selective increase in cardiac-related power.

The water-tower analogy of the cardiovascular system.

The cardiovascular system is a complex arrangement of hydraulic, yet living, components. The complexity of this system may make it difficult for students to see the "forest" instead of the "trees." To better explain the dynamics of cardiovascular function and control, an analogy has been drawn to the operation of a city water supply. In cities that use a water tower, fresh water is pumped up into the tower from a river or other source. The tower serves as a pressure reservoir for providing water to homes through a largely parallel arrangement of distribution pipes. Local homeowners control their own water usage through faucets, whereas the city maintains water pressure by monitoring the level in the tower. Key analogous points with the cardiovascular system are the heart as the city pump, the aorta as the water tower, arteries as parallel distribution pipes, and arterioles as faucets. Baroreceptor reflex control is discussed as well as such features as the capacitance role of veins, the skeletal muscle pump, and the competition between locally mediated vasodilation and sympathetically mediated vasoconstriction. Subjective student and peer evaluations have indicated that this analogy is effective in improving student comprehension of the cardiovascular system.

Medullary lateral tegmental field: an important synaptic relay in the baroreceptor reflex pathway of the cat

This study was designed to test the hypothesis that the medullary lateral tegmental field (LTF) is an important synaptic relay in the baroreceptor reflex pathway controlling sympathetic nerve discharge (SND) of urethan-anesthetized cats. We determined the effects of blockade of excitatory amino acid-mediated neurotransmission in the LTF on three indexes of baroreceptor reflex function: cardiac-related power in SND, strength of linear correlation (coherence value) of SND to the arterial pulse (AP), and inhibition of SND during increased arterial pressure produced by abrupt obstruction of the abdominal aorta. Bilateral microinjection ofd-(−)-2-amino-5-phosphonopentanoic acid, an N-methyl-d-aspartate (NMDA) receptor antagonist, abolished cardiac-related power and coherence of SND to the AP, and it prevented inhibition of SND during aortic obstruction. These data support the view that NMDA receptor-mediated neurotransmission in the LTF is critical for baroreceptor reflex control of SND. Bilateral microinjection of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo-[ f]-quinoxaline-7-sulfonamide, a non-NMDA receptor antagonist, decreased cardiac-related power and total power in the 0- to 6-Hz band of SND; however, the AP-SND coherence value remained high, and inhibition of SND during aortic obstruction was preserved. These data imply that non-NMDA receptor-mediated neurotransmission in the LTF is involved in setting the level of excitatory drive to sympathetic nerves.