Adrenergic neurotransmission in tail arteries from two-kidney, one clip, renal hypertensive rats.

Abstract

SUMMARY The goal of this study was to determine if increased vascular smooth muscle sensitivity to norepinephrine in two-kidney, one clip (2K1C) hypertensive rats is the result of a decrease in adrenergic nerve function. Vascular sensitivity to norepinephrine was measured in isolated tail artery strips from 2K1C hypertensive and normotensive rats and in various arterial strip preparations from normotensive rats that exhibit varying degrees of adrenergic innervation. In each case, the characteristic of the vascular smooth muscle response in the vessel with the least amount of adrenergic innervation simulated the response of the vascular smooth muscle from the 2K1C hypertensive rats. Release or displacement of endogenous norepinephrine by electrical stimulation, tyramine, potassium-free solution, and potassium excess, and measurement of tissue content of norepinephrine suggest that the blood vessels of 2K1C hypertensive animals are depleted of catecholamine stores. Based on these observations it is concluded that the increased sensitivity of vascular smooth muscle to norepinephrine in 2K1C hypertensive rats is the result of a diminished adrenergic innervation. This increased sensitivity of the vasculature may be a response of the smooth muscle cells to a decrease in innervation or the consequence of vascular wall hypertrophy leading to an increased number of smooth muscle cells that are remote from their adrenergic supply. (Hypertension 5:298-306, 1983 KEY WORDS * aorta • mesenteric artery * acute and chronic adrenergic denervation norepinephrine • cocaine * vascular sensitivity T HE junction between the adrenergic nerve ending and the smooth muscle cells of the blood vessel wall makes sympathetic control of vascular function possible. Experimental evidence developed over the past two decades may be interpreted as indicating that functional changes in this nerve-muscle relationship contribute to the increase in total peripheral resistance of experimental renal hypertension.1 " 3 Specifically, both catecholamine content 4 " 6 and catecholamine histofluorescence 7 -8 have been found to be significantly decreased in vascular beds of animals with both renal clip hypertension and renal hypertension induced by figure-eight parenchymal ligature technique. Ultrastructural studies 9 -10 indicate a decrease in the number of dense core vesicles in adrenergic nerve endings of arteries from renal hypertensive

Changes in α2-Adrenoceptors on Vascular Smooth Muscle and Neural Membranes following Hypertension Induced by Renal Ischemia

“…norepinephrine was also increased in these vessels [32], Increased vascular sensitivity in hypertensive rats to exogenous catechol amines has been reported previously. For example, Lais and Brody [33] found that the threshold constrictor response to norepi nephrine in the denervated hindquarters of spontaneously hypertensive rats is only one third that of NT rats.…”

“…An alternative explanation is the conversion of spare ct]-adrenoceptors, which Ruffolo and Yaden [35] have shown to be present in rat vasculature, to functional a r adrenoceptors. Such comparable increases in sensitivity may also suggest that: (i) in the tail artery, both extrajunctional ap and 012-adrenoceptors are stimulated by the same store of presynaptic norepinephrine, which is depleted in the RHT rat [32], or (ii) that sympathetic innervation to the tail arteries is decreased in the RHT rat, and that such a decrease has a comparable effect on neurons which stimulate extrajunctional Cb-adrenoceptors as well as neurons which stimulate extrajunctional ct|-adrenoceptors.…”

“…Al though this relationship has been the subject of considerable investigation [8,11,15,19,29], there is at the present little consensus as to the role which altered sympathetic inner vation plays in the development and/ or maintenance of hypertension. Indeed, whereas most authors have postulated that hypertension is a result of an increase in sympathetic influence on the vasculature [30,31 ], a study by Webb et al [32] provided evidence to support the hypothesis that in the 2-kidney-l-clip RHT rat, peripheral adrenergic innervation is actually decreased. These authors showed that in tail arteries from chronically hypertensive rats, there is a diminished release or displacement of en dogenous norepinephrine following elec trical stimulation, administration of tyramine or elevation of the extracellular con centration of potassium, which suggests de pletion of endogenous catecholamine stores.…”

Changes in the Vascular Reactivity of the Isolated Tail Arteries of Spontaneous and Renovascular Hypertensive Rats to Endogenous and Exogenous Noradrenaline

“…The case for potassium is more com plicated. Potassium-induced contractions of poorly innervated vascular smooth muscles, such as aorta, are independent of noradrena line release [Shibata and Carrier, 1967], Such contractions are not inhibited by aadrenoreceptor blocking agents such as phentolamine (10~4 A/) or by reserpine [Garret and Carrier, 1971], In the densely innervated rat tail artery, phentolamine (1 O'6 or 10-5 M) inhibits 35-50% of the vasocon striction induced by potassium [Webb et al, 1978[Webb et al, , 1983. We found that phentol amine (4 X 10~b M ) blocks potassium-in duced vasoconstriction (40 mM) by 95% [unpubl.…”

“…This leads to a general increase in the reactivity to a wide variety of vasoconstrictor agents. Others have reported, however, that whilst responses to exogenous noradrenaline are increased, vasoconstrictor responses to stimuli that release endogenous noradrena line are not modified [Lais et al, 1974;Collis and Vanhoutte, 1977], Likewise, it has been reported that renovascular hyper tension in the rat is accompanied by struc tural adaptation of the vessel wall similar to that occurring in the SHR [Lundgren et al, 1974] and that responses to endogenous and exogenous noradrenaline are different: there is a decrease in the response to en dogenous noradrenaline and an increase in the response to exogenous noradrenaline [Webb et al, 1983].…”