Role of catecholamines and vasopressin in cardiovascular responses to bilateral dorsolateral transection of the medulla oblongata in the rat.

Abstract

SUMMARY The role of sympathetic and other pressor systems in the development of fulminant hypertension induced by baroreceptor deafferentation is still unclear. We studied the effects of acute hypertension produced by bilateral dorsomedullary knife cuts lateral to the nucleus tractus solitarii (DMK-cut) on plasma norepinephrine (NE), epinephrine (E), and vasopressin (VP) in conscious, tailartery-cannulated rats. In saline-pretreated (SAL) rats, DMK-cut caused a significant (p < 0.001) rise in mean blood pressure (MAP, +68 ± 3 mm Hg), heart rate (HR, + 97 ± 19 bpm), NE ( + 2.5 ± 0.3 ng/ml), E (+ 2.7 ± 0.4 ng/ml), and VP (+115 ± 34 pg/ml) compared to sham-operated rats. Neither sympathetic blockade with chlorisondamlne (CHLO, 10 mg/kg, s.c.) nor elimination of the pressor effects of VP by use of Brattleboro rats or the VP pressor antagonist resulted in a maximal MAP response significantly different from that in the SAL + DMK-cut group. However, CHLO-pretreatment of Brattleboro rats completely abolished the increase in MAP and HR. It is suggested that the bilateral DMK-cut causes acute hypertension, probably due to the abolition of baroreceptor reflexes by central interruption of neural connections of the nucleus tractus solitarii. It appears that both the increased sympatboadrenomedullary activity and VP release normally contribute to this hypertension; however, either one is sufficient to sustain the elevated blood pressure. (Hypertension 5: 908-915, 1983) KEY WORDS • norepinephrine • epinephrine heart rate • neurogenic hypertension vasopressin • blood pressure O VER the past several years, peripheral or central interruption of baroreceptor reflex pathways has been shown to produce acute hypertension in several different species.1 " 6 In rats, Doba and Reis' have shown that bilateral electrolytic lesions of the nucleus tractus solitarii (NTS) rapidly produce fulminating arterial hypertension. Intense vasoconstriction in specific systemic vascular beds causes a marked increase in total peripheral resistance; this reduces cardiac output and eventually leads to pulmonary edema.7 Similar cardiovascular responses have been produced in rats by dorsolateral medullary knifecut (DMK-cut) lateral to the NTS. 8 A number of mechanisms appear to contribute to this acute and extreme elevation of blood pressure. It has been suggested that hypertension due to NTS lesions is a result of a marked augmentation of sympathetic neuronal discharge, 1 ' 2 4 5 since ganglionic and alpha-adrenergic blockade reverses the pressor re-

Selective cardiovascular and neuroendocrine effects of a kappa‐opioid agonist in the nucleus tractus solitarii of rats.

“…In addition, we have shown that the rise in blood pressure which follows bilateral U50488H injections is associated with a marked increase in the level of circulating AVP. The possibility that the increase in blood pressure is mediated by a direct vasoconstrictor action of AVP is supported by recent studies showing that AVP functions as a rapidly acting and potent factor in both the recovery ofblood pressure following haemorrhage (Laycock, Penn, Shirley & Walter, 1979;Zerbe, Bayorh & Feuerstein, 1982; 372 OPIOIDS AND NUCLEUS TRACTUS SOLITARII Feuerstein, Bayorh, Zerbe & Kopin, 1984), and in the development of pressor responses (Hatzimkolaou, Gavras, Brunner & Gavras, 1981;Zukowska-Grojec, Bayorh, Zerbe, Palkovits & Kopin, 1983). Definitive evidence for a vasoconstrictor action ofAVP in the present study is lacking, but the results ofthe phenoxybenzamine experiments clearly indicate that sympathetic activation is not involved in the development of the U50488H-induced response.…”

“…Furthermore, the K-agonist response appears to be specific since a 8-opioid agonist elicited similar effects in Brattleboro and Long-Evans rats, and the &-agonist pressor response was not significantly altered by the AVP antagonist, but was completely blocked by phenoxybenzamine. The possibility that the differential action of U50488H in Brattleboro and Long-Evans rats and the AVP antagonist blockade may be explained by central autonomic effects of AVP in the nucleus tractus solitarii (Matsuguchi, Sharali, Gordon, Johnson & Schmid, 1982;Pittman, Lawrence & McLean, 1982) cannot be ruled out, but such action appears unlikely in view of the observation that the cardiovascular response to centrally administered AVP is not dependent upon AVP release from the pituitary (Pittman et al 1982) and the demonstration that the dose of AVP antagonist which blocked the K-agonist pressor response by approximately 50 % has been shown previously (Kruszynski, Lammek, Manning, Seto, Haldar & Sawyer, 1980) Zerbe & Kopin, 1984), and in the development of pressor responses (Hatzimkolaou, Gavras, Brunner & Gavras, 1981;Zukowska-Grojec, Bayorh, Zerbe, Palkovits & Kopin, 1983). Definitive evidence for a vasoconstrictor action ofAVP in the present study is lacking, but the results ofthe phenoxybenzamine experiments clearly indicate that sympathetic activation is not involved in the development of the U50488H-induced response.…”