Jennifer E. Angell-James

Characteristics of Single Aortic and Right Subclavian Baroreceptor Fiber Activity in Rabbits with Chronic Renal Hypertension

Experimental renal hypertension was induced in rabbits by wrapping polyethylene around one kidney and removing the other. The impulse activity in single baroreceptor fibers of the aortic nerves to the aortic arch and the right subclavian areas was studied 7–19 weeks postoperatively during nonpulsatile perfusion of an isolated aortic arch preparation. The results were compared with those obtained in normal rabbits. Curves relating the impulse frequency to the aortic arch pressure were constructed. In rabbits with hypertension, the threshold pressure of the aortic baroreceptor fibers was increased from a normal value of 52.5 ± 5.5 to 106.5 ± 5.8 mm Hg, and the point of inflection was increased from 112.4 ± 6.2 to 163.4 ± 5.1 mm Hg. The sensitivity of the baroreceptors to changes in pressure was reduced from 1.19 ± 0.14 to 0.64 ± 0.06 impulses/sec mm Hg−1. Similar results were obtained for the right subclavian area. Hysteresis, as indicated by the separation of the curves produced by first increasing and then reducing the aortic pressure, was more evident in rabbits with hypertension than in normal rabbits. The changes in baroreceptor activity in rabbits with hypertension were associated with alterations in the mechanical properties of the arterial walls, which were demonstrated by the pressure-volume curves. Also, there were demonstrable histological lesions of the arterial walls and the receptors in rabbits with hypertension.

Arterial baroreceptor activity in rabbits with experimental atherosclerosis

A total of 16 rabbits developed atherosclerosis after receiving a diet containing 1% cholesterol and 6% sunflower seed oil for up to 67 weeks. Their mean blood pressure rose from 85 to 114 mm Hg. The aortic arch region was isolated and perfused with Krebs-Henseleit solution, and the impulse activity of 70 single aortic and 8 right subclavian baroreceptor fibers was studied during step increases and decreases in perfusion pressure. The threshold pressure of the aortic baroreceptor fibers from the atherosclerotic rabbits was only slightly higher (P > 0.4) than that of 29 fibers from 17 normal rabbits, but the impulse frequency was less (P < 0.02). The gradient of the impulse frequency-pressure curves (0.73 impulses/sec mm Hg−1), was significantly lower (P < 0.01) than normal (1.19 impulses/sec mm Hg−1), as was the gradient of the curves from the right subclavian baroreceptor region. The curves resulting from first increasing and then decreasing the perfusion pressure were more separated in the atherosclerotic rabbits than they were in the normal rabbits. There was a correlation between the amount of the reduction in the sensitivity of the aortic baroreceptors and the length of time the rabbits had been on the lipemic diet (r = 0.96). The changes in the baroreceptor activity were associated with a reduction in the distensibility of the perfused area and with histological lesions in the baroreceptors and the arterial walls. The mild hypertension in the atherosclerotic rabbits could partly be accounted for by the reduction in aortic baroreceptor activity. Similar mechanisms might contribute to blood pressure anomalies in humans with atherosclerosis.

Some Aspects of Upper Respiratory Tract Reflexes

Respiratory and cardiovascular reflexes have been elicited from receptors in the nose and larynx in the anaesthetized dog. Cigarette smoke in the nose causes reflex apnoea, bradycardia and vasoconstriction, probably due to systemic absorption through the nose. Stimulation of laryngeal nerve also results in reflex apnoea, bradycardia, and limb vasoconstriction. When asphyxia supervenes due to apnoea, stimulation of the carotid body chemoreceptors occurs which normally cause, as primary effects, hyperpnoea and bradycardia. However, it has been shown that stimulation of the laryngeal receptors inhibits the carotid body respiratory reflex and facilitates the carotid body cardio-inhibitory reflex, the latter leading to temporary cardiac arrest. The clinical implications of this finding are discussed.

The effects of artificial lung inflation on reflexly induced bradycardia associated with apnoea in the dog

1. The cardiac effects of artificial inflation of the lungs were studied during reflexly induced apnoea and bradycardia in anaesthetized dogs.

The interaction of reflexes elicited by stimulation of carotid body chemoreceptors and receptors in the nasal mucosa affecting respiration and pulse interval in the dog

1. The effects on respiration and pulse interval of stimulation of the carotid body chemoreceptors before, during and after stimulation of receptors in the nose have been studied in the anaesthetized dog.

Cardiorespiratory control by carotid chemoreceptors during experimental dives in the seal

The diving responses of apnea and bradycardia, produced experimentally by immersing the face in water, were successfully elicited in the harbor seal Phoca vitulina anesthetized with urethan. The role of the carotid body chemoreceptors in the production of the diving bradycardia was studied in isolated carotid sinus-body preparations autoperfused with blood from the arterial circulation. When asphyxia was well developed during a dive the chemoreceptor drive was withdrawn by temporarily perfusing the chemoreceptors with blood of high PO2 (greater than 400 mmHg) and normal PCO2 from a disk oxygenator. The heart rate immediately rose to its predive value. Reestablishing hypoxic hypercapnic blood perfusion of the chemoreceptors from the animals own circulation caused bradycardia with persistence of the apnea. Breathing restarted only on emersion. Substitution of normal arterialized blood from the oxygenator before or at the onset of a dive had no effect on the existing heart rate. It is concluded that the carotid bodies play an important part in maintaining the diving bradycardia during developing asphyxia without affecting respiration.

Pathophysiology of Aortic Baroreceptors in Rabbits with Vitamin D Sclerosis and Hypertension

Calciferol (vitamin D2) (50,000–100,000 IU) and calcium lactate (1 g) were added to the normal diet of 22 rabbits for 7–11 days. When mean arterial blood pressure had risen from a control value of 87.2 ± 3.7 mm Hg to an experimental value of 137.8 ± 5.7 mm Hg (11–145 weeks), the aortic arch of 9 of these rabbits was isolated and perfused with Krebs-Henseleit solution. The impulse activity in 75 aortic baroreceptor fibers from the left aortic nerve was studied during nonpulsatile perfusion at different pressures and was compared with the impulse activity in 29 fibers from 17 normal rabbits. The threshold pressures and the pressure at the point of inflection of the curves were lower in these fibers than they were with fibers from normal rabbits. The gradient of the curves relating baroreceptor impulse frequency to aortic pressure was depressed from a normal mean value of 1.19 impulses/sec mm Hg−1 to 0.61 impulses/sec mm Hg−1 (P < 0.001). A similar depression of the gradient was found in 7 baroreceptor fibers from the right aortic nerve. The change in the sensitivity of the baroreceptors was more closely related to the time interval after the calciferol treatment (r=−0.95) than it was to the mean arterial blood pressure (r= −0.76). The pressure-volume curves show that it was also related to the decreased distensibility of the aortic arch region. Histologically, the aortic arch region had extensive medial sclerosis with calcification.

Baroreflex Sensitivity in Rabbits During the Development of Experimental Renal Hypertension and Medial Sclerosis

Baroreflex sensitivity was assessed in 9 normotensive (N), 8 renal wrap (one kidney model, RH) and 16 medial sclerotic rabbits (MS, fed on calciferol 50,000 i.u. and calcium lactate 1g for 10 days) before (mean BP;N, 79 +/- 3.3 mm Hg; RH, 80 +/- 7.4 mm Hg; and MS, 83 +/- 1.0 mm Hg) and at monthly intervals for up to 16 weeks after the induction of the disease processes (mean BP;N, 87 +/- 3.9 mm Hg; RH, 127 +/- 7.2 mm Hg and MS, 99 +/- 3.8 mm Hg). Blood pressure was elevated by i.v. phenylephrine (5 and 10 micrograms.kg-1) or angiotensin (250 ng.kg-1) and baroreflex sensitivity assessed by the increase of pulse interval per unit rise of pressure. The pressor response was greater in the RH and MS than in the N rabbits. The baroreflex sensitivity showed a progressive reduction with time and with the elevation of blood pressure in both MS and RH rabbits. The difference was significantly greater (P < 0.01) than in the aged related control rabbits (P < 0.05). There was an inverse relationship between baroreflex sensitivity and the pressor response in MS rabbits. Results indicated progressive baroreceptors dysfunction in hypertensive and medial sclerotic rabbits.

Cardiovascular and respiratory effects of carotid body stimulation in the monkey.

1. The carotid bodies were stimulated in the anaesthetized pig‐tailed macaque monkey (M. nemestrina) using (i) brief injections of cyanide or CO2‐equilibrated bicarbonate solution into a common carotid artery, and (ii) longer perfusion with hypoxic hypercapnic blood in vascularly isolated chemoreceptor preparations.

Respiratory and Cardiovascular Responses to Hyperoxia, Hypoxia and Hypercapnia in the Renal Hypertensive Rabbit: Role of Carotid Body Chemoreceptors

We tested the hypothesis that in renal hypertension the increased peripheral vascular resistance of neurogenic origin might be due to a reflex through resetting of the carotid body chemoreceptors. The reflex respiratory and cardiovascular functions of the carotid bodies were studied in a one-kidney wrapped hypertension model in conscious rabbits, and compared with a control group of animals, by breathing 100% oxygen, three hypoxic gas mixtures to which were added sufficient CO2 to maintain the PaCO2 constant, and 2 and 4% CO2 in 21% O2 and N2. In the control state (breathing room air) the renal hypertensive animals had a slightly higher respiratory minute volume, a higher level of arterial blood pressure and increased calculated systemic vascular resistance, compared with the normal group, but there was no difference in cardiac output. Hyperoxia had no consistent effect on respiration, heart rate or arterial blood pressure. Increasing degrees of isocapnic hypoxia caused the same degree of hyperventilation and bradycardia in both groups of animals. The arterial blood pressure did not change in either group but there was a transient increase in systemic vascular resistance in the renal hypertensives breathing 9 and 7.5% O2. The respiratory responses to 2 and 4% CO2 were similar in the two groups of animals. In the renal hypertensive animals, serial sections of the carotid bodies showed pathological changes, including subendothelial proliferation in vessels supplying the carotid bodies with narrowing of their lumens, fragmentation of the elastic laminae of the media, hypertrophy of the smooth muscle and extensive fibrosis with occasional haemorrhages. The capillaries, however, were normal. The rostral-caudal lengths of the carotid bodies were similar in the two groups. In view of our findings we conclude that the relatively normal carotid chemoreceptor responses in renal hypertensive rabbits may, in part at least, be the result of the carotid body blood flow through the partially occluded vessels being maintained at near normal levels by the elevated blood pressure.