Possible sex differences in autonomic regulation of the heart were studied by injecting standard hypotensive doses of histamine or bradykinin to induce reflex tachycardia in awake rats. Although depressor responses to both drugs were unaltered, the tachycardia was greatly reduced by beta-adrenergic blockade with propranolol and abolished almost completely after combined blockade with propranolol and atropine. These findings indicate that the tachycardia was mostly due to increased sympathetic stimulation wiht a minor contribution from parasympathetic withdrawal. With large doses of bradykinin, direct myocardial stimulation also seemed likely, since some residual tachycardia remained even after combined blockade. Reflex tachycardia was generally more pronounced in male than in female rats. Because males had lower base-line heart rates and more tachycardia that was resistant to beta-adrenergic blockade than females, autonomic regulation was concluded to be predominantly parasympathetic in males and sympathetic in females. Whereas the exact cause of these variations in chronotropic regulation is unknown, it was considered possible that differences in sex hormones may have affected sensitivity of some component of the reflex arc.

When drug effects are quantified using the tail-cuff method, changes in systemic arterial pressure are extrapolated from those occurring in the caudal artery. The validity of this extrapolation was tested in anesthetized rats by recording drug-induced changes in phasic arterial pressure simultaneously from catheters inserted into the lower abdominal aorta, carotid, and caudal arteries. Pressor responses to norepinephrine or angiotensin were of equal magnitude at all three sites, but phentolamine reduced systolic pressure in the aorta or caudal artery more than that in the carotid artery. Unlike previous discrepancies between carotid and tail-cuff systolic pressures, aortic hypotension caused by injections of phentolamine or pentolinium in awake normotensive or spontaneously hypertensive rats was accurately predicted by the tail-cuff method. Because drug-induced changes in diastolic pressure always varied much less than those in systolic pressure, should indirect measurement of diastolic pressure become technically feasible, it might be preferable for assessing drug effects on blood pressure.

Although salicylate intoxication continues to be a common clinical problem, especially in pediatrics, relatively few studies have been carried out on the cardiovascular effects of salicylates. A report of Tenney and Miller (1) is perhaps the most cited reference that deals with the circulatory effects of salicylates, yet that work was performed before beta adrenergic blocking agents were available. Tenney and Miller (1) concluded that salicylates have a direct stimulating action on cardiac muscle which probably is independent of autonomic nervous activity. For the most part the cardiovascular effects of salicylates have been studied in the anesthetized dog (1, 2); there is growing evidence, however, that the conscious dog responds to certain physiological and pharmacological stimuli in a manner quite different from that of the anesthetized dog (3). For the above reasons, we have examined in detail the cardiovascular and acid-base responses that are elicited by the intravenous infusion of large doses of sodium salicylate into the conscious dog.Methods. Experiments were performed on conscious mongrel dogs weighing an average of 13 kg. Each dog was prepared for the experiments during a preliminary operation under anesthesia with sodium pentobarbital (25 mg/kg body weight with supplements as required). The chest was entered aseptically on the left side, and a flow probe was placed around the ascending aorta. Vinyl catheters were placed in the descending aorta, pulmonary artery, and superior vena cava by the technique of Herd and Barger (4). In addition, a catheter was inserted into the left atrium through a small tributary of a pulmonary vein. The proximal ends of the catheters and flow probe cable emerged from the skin adjacent to the spinal column and were embedded in a Styrofoam block, The wound was closed with sutures and sealed with a spray dressing. During the operation each animal received 500 ml of 5% dextrose in water iv; this solution also contained one million units of aqueous penicillin G. Postoperatively, the animals received 300,000 U of procaine penicillin G im daily for 5 days. All catheters were flushed with saline three times each week and filled with a solution of sodium heparin in saline (1000 U/ml). A nylon jacket protected the catheters and flow probe.Each dog was allowed to recover from the operation for at least 1 week and was trained to rest quietly in an animal stand. During each experiment pressures in the aorta, pulmonary artery, left atrium, and superior vena cava were monitored continuously using Statham P23Db transducers. Cardiac output was measured with an electromagnetic flowmeter and a circuit that automatically zeroed the baseline of aortic flow on a beat-to-beat basis (5). All pressures and flow signals were recorded on an oscillographic recorder. Data were analyzed by an automatic data averager that accurately computed the time-integrated mean value of up to seven inputs and printed a copy of the results (6). Total peripheral vascular resistance and pulmonary vascular resistance w...

Contrasting with the hypertension resulting consistently after DOCA implantation, mature female rats given Enovid daily for 20 weeks had only slight and occasional increases in blood pressure. The pressure elevations remained infrequent and transient even when drinking water was replaced with isotonic saline solution but they became more pronounced when Enovid treatment was initiated at an earlier age. Despite the failure to cause sustained hypertension, the data indicate that Enovid affects blood pressure and that both mestranol and norethynodrel are essential for this effect. Pressor responses to norepinephrine or angiotensin were unaffected even after 20 weeks of pretreatment but those to electrical stimulation of the posterior hypothalamus were increased in rats pretreated with Enovid. Enhanced responsiveness to hypothalamic stimulation occurred only in the awake state and was not demonstrable after the central nervous system (CNS) had been depressed with urethane. These results can be explained by an increased sensitivity of hypothalamic pressor areas produced by Enovid prior to the development of hypertension and the mechanisms involved may be similar to those occurring in spontaneously-hypertensive rats. However, the possibility of hypersensitivity at other sites in the sympathetic vasomotor outflow cannot be ruled out.