Production of sustained hypertension by lesions in the nucleus tractus solitarii of the American foxhound.

Abstract

SUMMARY The purpose of this study was to develop a model of sustained neurogenic hypertension in the dog. Thirteen female American foxhounds (mean arterial pressure 105 ± 12 mm Hg) with Indwelling arterial and venous cannulas were maintained on a constant 82 mEq/day sodium intake. After a control period of at least 10 days, under pentothal anesthesia and direct visualization, the animals had placement of bilateral electrical lesions of the nucleus tractus solitarii (NTS) at the level of the obex. After recovery from anesthesia, the dogs could be divided into two groups on the basis of blood pressure response. Group I (n = 6) developed sustained hypertension with an increase of mean arterial pressure of 25-35% above control values (p < 0.01) for 10 days after placement of the lesions. Group II (n = 7) had a transient increase of blood pressure on postoperative Day 1 but became nonnotensive for the subsequent 9 days of observation. The bemodynamic features of the dogs in Group I were increased total peripheral resistance, decreased cardiac output and slightly decreased heart rate; these changes were reversed to control by pbetolamine. Plasma renin activity, aldosterone concentration and blood pressure response to SQ20,881 were unchanged by NTS lesions. Group I dogs had sodium retention on postoperative Day 1, but no change in renal plasma flow or glomerular filtration rate was observed during the chronic hypertensive phase. One Group I dog remained hypertensive for 8 weeks. All dogs in Group I were hypertensive and all in Group II were nonnotensive at sacrifice. Histologic sections from Group I dogs showed complete cellular destruction of the nucleus and the tractus solitarius bilaterally at the obex. In Group II, unilateral or incomplete cellular destruction of the NTS at the obex, or bilateral NTS lesions caudal to the obex were present.Bilateral NTS lesions at the obex in the American foxhound result in sustained arterial hypertension characterized by increased peripheral sympathetic nervous system activity and lack of dependence on the renin-angiotensin-aJdosterone system. (Hypertension 1: 246-254, 1979) KEY WORDS • hypertension • central nervous system • nucleus tractus solitarius • dog • renin-angiotensin system • catecholaminesT HE sympathetic nervous system may play a critical role in the initiation and/or maintenance of several models of hypertension in experimental animals and possibly also of essential hypertension in man. The lines of evidence include correlation of sympathetic nerve activity with blood pressure as spontaneously hypertensive rats develop hypertension; 1 production of sustained hypertension by continuous stimulation of renal and splanchnic

Hemodynamic responses to bilateral lesions of the nucleus tractus solitarii in spontaneously hypertensive and normotensive rats.

“…This was also found in conscious, normotensive Sprague-Dawley rats 1 and dogs. 17 ' 1B The CO reduction in WKY and NR was also in agreement with previous findings in normotensive animals, 1 but this is the first report of the response of the cardiac output to NTS lesion in SHR. Indeed, CO was not significantly lower than that of sham-lesioned rats.…”

Catecholamine Release–Inhibitory Peptide Catestatin (Chromogranin A 352–372 )

“…Because baroreflex sensitivity is diminished in both established hypertension and the stillnormotensive offspring of patients with hypertension, 32,34 alterations of this trait in hypertension cannot be simply a response to hypertension but might be involved early in the pathogenesis or development of the disease trait. In experimental animals, lesions of the baroreceptor afferent nerves or central nuclei [35][36][37] may result in sustained hypertension. More recently, Lohmeier et al 38 showed that chronic activation of the baroreflex produces sustained reductions in BP and sympathetic activity in animals.…”

Chronic lability of the arterial blood pressure produced by electrolytic lesions of the nucleus tractus solitarii in the rat.

“…Lesions of the NTS produced a significant increase in the average level and lability of the MAP in cats (Nathan and Reis, 1977) and an elevated MAP in dogs which may or may not be associated with increased lability (Laubie and Schmitt, 1979;Carey et al, 1979). Cowley et al (1973Cowley et al ( , 1980 have suggested that the elevated MAP reported in many of the studies resulted from increased responsiveness of debuffered animals to environmental stimuli and the methods used to record cardiovascular responses.…”