Adenosine triphosphate attenuates renal sympathetic nerve activity through left ventricular chemosensitive receptors.

We previously reported that ATP, but not adenosine, administered i.v. attenuates the baroreflex-mediated increase in sympathetic nerve activity in response to arterial hypotension by a vagal afferent mechanism. It was not elucidated in that study which vagal afferent endings are involved. Mongrel dogs were anesthetized with alpha-chloralose, thoracotomy was performed and a 27-gauge hypodermic needle was inserted into the left circumflex coronary artery. The left renal sympathetic nerves were isolated and placed on a bipolar silver electrode for measurement of renal sympathetic nerve activity (RSNA). Dose-response effects of intracoronary or i.v. infusion of ATP (100, 200 or 400 microg/kg/min) on RSNA and mean arterial pressure were studied in neuraxis-intact and cervically vagotomized dogs. RSNA was increased dose-dependently with decreasing mean arterial pressure during the i.v. ATP infusion. Elevation of RSNA was attenuated by higher intracoronary ATP infusion rates, despite the fact that mean arterial pressure was decreased dose-dependently. Left ventricular end-diastolic pressure, however, remained unchanged. This suppression of RSNA by the intracoronary ATP infusion was completely abolished by bilateral cervical vagotomy. Our data suggest that ATP attenuates reflex increases in sympathetic nerve activity by possibly stimulating ventricular chemoreceptors with cardiac vagal afferents.

Vagal involvement in the action of exogenous adenosine triphosphate on reflex renal sympathetic nerve activity.

The reason why adenine compounds when used as hypotensive agents are devoid of significant reflex sympathetic activity, such as rebound hypertension and tachycardia, is not clearly understood. This study, performed on alpha-chloralose-anesthetized dogs, examined, first, the effects of adenosine triphosphate (ATP) and adenosine as compared with those of sodium nitroprusside on efferent renal sympathetic nerve activity (RSNA), as an indicator of general reflex sympathetic activity, and second, whether vagal involvement could be demonstrated in the action of ATP and adenosine on RSNA. Renal sympathetic nerve activity increased progressively with increasing doses of sodium nitroprusside (5, 10, and 20 micrograms/kg) and adenosine (0.5, 2.0, and 4.0 mg/kg), whereas ATP suppressed RSNA at 2.0 and 4.0 mg/kg. High doses of ATP and adenosine (4.0 mg/kg) were injected into intact (n = 7) and vagotomized dogs (n = 7). Both ATP and adenosine induced rapid onset of hypotension without rebound hypertension and tachycardia. After vagotomy, the attenuation of RSNA by ATP was completely abolished and rebound hypertension and tachycardia were observed. Vagotomy did not alter the effect of adenosine on RSNA. It is concluded that ATP-induced hypotension is associated with attenuation of sympathetic efferent nerve activity mediated through vagal afferent pathways. Vagal afferent impulses are thought to be one of the mechanisms that inhibit reflex sympathetic activities, such as rebound hypertension after ATP-induced hypotension. The mechanisms by which adenosine inhibits reflex sympathetic activity are not, however, secondary to vagal afferent involvement and must be multifactorial.

Attenuation of arterial baroreceptor reflex response to acute hypovolemia during induced hypotension.

Preservation of the arterial baroreflex response is important to restore cardiac output and blood pressure by reflex sympathetic nerve activation in the event of sudden hypotension caused by acute blood loss during surgery. However, the arterial baroreflex may be significantly attenuated by both anesthetics and hypotensive agents. In isoflurane-anesthetized dogs, the authors investigated the arterial baroreflex response 1) to bolus injections of sodium nitroprusside (SNP), prostaglandin E1 (PGE1) and trimethaphan (TM); and 2) to rapid blood loss (5 ml/kg) before and during induced hypotension with SNP, PGE1, and TM by measuring mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). Hypotension produced by both SNP and PGE1 was accompanied by an increase in RSNA and HR. The increase in RSNA and HR following the SNP bolus injection was significantly greater than that following injection of PGE1 (P less than 0.05). Trimethaphan was associated with a decrease in RSNA and HR. Rapid blood loss resulted in the same degree of MAP reduction (20 +/- 2 mmHg) before and during induced hypotension. Sensitivities of baroreflex, as evaluated by ratios of maximum changes in RSNA or HR to MAP (delta RSNA/delta MAP, delta HR/delta MAP), in response to rapid blood loss, were significantly suppressed during continuously induced hypotension, as compared with responses before induced hypotension. Despite the same degree of induced hypotension (70 +/- 5 mmHg of MAP), delta RSNA/delta MAP and delta HR/delta MAP in response to rapid blood loss were significantly greater with PGE1 than those with SNP (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Baroreceptor reflex response to acute blood loss during induced hypotension--a comparison of sodium nitroprusside, prostaglandin E1 and trimethaphan].

This experiment was designed to evaluate the reflexive heart rate (HR) response to acute blood loss during sodium nitroprusside (SNP), prostaglandin E1 (PGE1) and trimethaphan (TM) induced-hypotension in isoflurane anesthetized dogs. Reflexive increase in HR to acute blood loss was significantly greater during PGE1 induced-hypotension than during that with SNP. TM inhibited the reflexive HR response to acute blood loss. These results suggest that PGE1 induced-hypotension provides a safer margin than that with SNP and TM when rapid bleeding occurs during anesthesia and surgery.

Alteration of red cell deformability during extracorporeal bypass: membrane v bubble oxygenator.

Red cell deformability is essential for normal microcirculation, since the red cell is greater in diameter than the caliber of small capillaries. Red cell filtration rate (RFR) was measured using a 5 microns nucleopore polycarbonate filter as an index of red cell deformability before, during, and after two hours of extracorporeal circulation for coronary artery bypass surgery, with a bubble oxygenator (eight patients) or a hollow fiber membrane oxygenator (14 patients). RFR decreased steadily and significantly during bypass in the bubble oxygenator group. After the start of bypass, RFR was significantly higher at all measurement intervals in the membrane oxygenator group as compared with the bubble oxygenator group. It can be postulated that significantly impaired red cell deformability caused by the bubble oxygenator is attributed to mechanical damage secondary to a huge blood-gas interface, and possibly to neutrophil-mediated oxygen free radical formation due to complement activation. Results indicate that the hollow fiber membrane oxygenator is superior to the bubble oxygenator in maintaining red cell deformability.