Sympathetic cross-innervation of SHR and genetic controls suggests a trophic influence on vascular muscle membranes.

Abstract

We have attempted to differentiate neural from humoral environmental factors as the cause of altered arterial muscle membrane properties in spontaneously hypertensive rats (SHR). This laboratory has previously reported that alterations in membrane electrical properties appear to be responsible for increased NE sensitivity in caudal arteries from SHR. In this study, caudal arteries were transplanted into innervated or denervated anterior eye chambers of the same (KNR in KNR, SHR in SHR) or the opposite (KNR in SHR, SHR in KNR) strain. Seven weeks later, we measured membrane potential (Em) and norepinephrine (NE) contractile sensitivity (EC50) in both transplanted and host caudal arteries. Caudal arteries from 2-week-old donor animals transplanted into hosts reinnervated and developed Em and NE EC50 values characteristic of the host strain, interconverting between SHR and KNR characteristics in cross-transplantations. In other experiments, the superior cervical ganglion ipsilateral to the transplanted eye chamber was removed 1 day before transplantation to eliminate the influence of sympathetic nerves. Em values were the same in transplants denied sympathetic innervation whether the arteries were transplanted into the same or opposite strains. Although denervation increased NE sensitivity of KNR caudal arteries, sensitivity of arteries from the SHR strain was unchanged. Therefore, without sympathetic reinnervation, there was no interconversion of Em or NE EC50 characteristics between SHR and KNR by cross-transplantation. These results suggest that neural factors control the development of membrane properties of vascular muscle. It appears that the sympathetic nervous system of the SHR has altered trophic influences that contribute importantly to altered membrane properties in hypertension.

Trophic interactions between rat nerves and blood vessels in denervated peripheral arteries and in anterior eye chamber transplants.

“…The reinnervation of the tail artery segments transplanted into the sympathectomized anterior chamber was not anticipated, since transplants of this vessel have been described as "non-innervated" following ganglionectomy (Abel and Hermsmeyer, 1981). Similarly, Olson et al (1983) state that sympathetically noninnervated tissues will remain noninnervated in the eye, but do not consider the possibility of aberrant innervation of tissues which normally are sympathetically innervated.…”

“…As this site is immunologically privileged, the transplanted tissue is not rejected, and may become innervated by an ingrowth of neurons due to iridean nerve sprouting. In addition, this host site can be freed of sympathetic nerves through superior cervical ganglionectomy which destroys the adrenergic innervation of the iris (Abel and Hermsmeyer, 1981;Kobayashi et al, 1983;Olson et al, 1983).…”

Membrane mechanisms in arterial hypertension.

“…The second bit of evidence is that the SHR form of hypertension is the only one so far tested that is not prevented by the lesion of the anteroventral region of third ventricle (AV3V) developed by Brody and colleagues (Brody 1 )-It thus appears that, in SHR, neural factors and the trophic influence of the sympathetic nervous system are more important factors. The trophic influence is suggested because it was possible to demonstrate by cross-innervation experiments that the altered membrane NE sensitivity and E m electrogenesis follow the innervation, rather than the source animal for the caudal arteries (Abel and Hermsmeyer 49 ). There does not appear to be evidence that the SHR is dependent upon a humoral ouabain-like factor.…”

Contractile Response to Sympathetic Innervation in Neonatal Ventricular Cardiomyocytes of the Spontaneously Hypertensive Rat

“…We have shown that in vitro sympathetic innervation causes substantial improvement in contractile function of cultured ventricular cardiomyocytes from newborn WKY (9). Sympathetic innervation also determines the vascular muscle phenotype of arterial segments transplanted between WKY and SHR through a trophic influence (10). Similarly, extracts of hypertrophic cardiac muscle from SHR can induce cardiac hypertrophy (1 1).…”

“…Similarly, extracts of hypertrophic cardiac muscle from SHR can induce cardiac hypertrophy (1 1). Cardiac and vascular muscle from young SHR also exhibit increased sensitivity to adrenergic agonists (1 [2][3][4][5][6][7][8][9][10][11][12][13][14]. Based on these findings, we proposed that interstrain cellular differences in contractile function and in response to sympathetic innervation could produce a quantitatively different contractile effect in SHR that mav in Dart account for the cardiac derange-, .…”