Norepinephrine overflow in perfused mesenteric arteries of spontaneously hypertensive rats.

Abstract

We examined the overflow of endogenous norepinephrine with electrical stimulation, the associated pressor response, and rate of initial neuronal uptake of [ 3 H] norepinephrine in perfused mesenteric arteries of 7-and 13-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The tissues of two rats, a spontaneously hypertensive and a WKY control rat, were simultaneously processed and subjected to the same electrical stimulation. Both absolute and fractional overflow of endogenous norepinephrine during periarterial nerve stimulation (5 and 10 Hz for 1 minute) in the tissue of 7-week-old SHR was significantly greater whereas overflow of 13-week-old SHR was equivalent as compared with that of the age-matched WKY rats. The tissue content of norepinephrine was 20-25% higher in SHR of both ages. There was significantly enhanced [ 3 H] norepinephrine uptake in the tissues of young SHR, but no difference was observed in the older SHR. The pressor response to periarterial nerve stimulation was significantly enhanced in 7-week-old SHR and much more so at the older age as compared with the WKY control rats. Exogenous norepinephrine dose-response curves in the tissues of 7-week-old SHR exhibited a parallel leftward shift, characteristic of a change in sensitivity, whereas that of 13-week-old SHR showed a much steeper slope as compared with the respective WKY control rats. This finding suggests that in addition to smooth muscle supersensitivity, structural alterations had occurred in vasculature of 13-week-old SHR. These data indicate that in SHR both the exocytotic release of norepinephrine and the responsiveness of the vascular smooth muscle cells are enhanced in the developmental stage of hypertension whereas smooth muscle supersensitivity to norepinephrine and nonspecific structural alterations primarily contribute to the maintenance of hypertension at 13 weeks of age. {Hyperten-sion 1989;14:44-53)

In vitro perfusion studies of resistance artery function in genetic hypertension.

“…6 " 8 In hypertension there is evidence for changes in vascular responsiveness, such as increased reactivity to vasoconstrictors 9 and reduced net relaxation responses to the endothelium-dependent dilator acetylcholine. 1012 Also, there is increasing evidence that the sympathetic nervous system plays a role in the development and maintenance of hypertension, 13 " 15 and neuronal amine uptake appears to be greater in the spontaneously hypertensive rat (SHR) 1618 and human essential hypertension. 19 Changes in vascu-lar responsiveness have been ascribed to modifications in the arterial wall such as medial hypertrophy and hyperplasia, 20 which are the adaptive hallmarks of hypertension and which result in medial encroachment on the lumen.…”

Arterial neuroeffector responses in early and mature spontaneously hypertensive rats.

“…8 After vascular sympathetic stimulation, the absolute release of norepinephrine is greater in the SHR compared with WKY rats. 910 When norepinephrine overflow is normalized for the tissue concentration of the amine, a greater fractional release occurs in the mesentery of young SHR with normal release in older rats, 11 which may contribute to the development of hypertension. However, there is also evidence to indicate that fractional release of norepinephrine is only elevated in chronically hypertensive SHR.…”

Altered Calcium Handling in Peripheral Nerve Terminals and Blood Vessels in Spontaneously Hypertensive Rats

“…Our previous data show that isolated mesenteric nerve endings had increased NE release in young SHR/Izm [3] and that their hyperactive condition was suppressed more by calcium antagonist compared with normal rats [2]. In peripheral nerve endings, N-type calcium channels play an important role in NE release, although P/Q-type calcium channels also participate.…”

“…Animals were handled according to the institutional guidelines for animal research of Wakayama Medical University. An isolated mesenteric arterial preparation was made as previously reported [3]. Briefly, polyethylene tubes were inserted into the superior mesenteric artery and the mesenteric artery-intestine loop preparation was perfused with Krebs-Henseleit solution.…”

“…In our previous studies, we reported that spontaneously hypertensive rats (SHRs) had high plasma norepinephrine (NE) levels [1], similar to hypertensive patients [2], and that young SHRs had increased NE overflow from nerve endings in the mesenteric arteries [3]. In a series of publication, mechanisms of hypertension of SHR were similar to essential hypertension and WKY strain was commonly used as normotensive controls.…”