Cardiovascular hypertrophy and "waterlogging" in coarctation hypertension. Role of sympathoadrenergic influences and pressure.

Abstract

SUMMARY The abdominal aorta above the renal arteries was partially constricted or sham-constricted in rats age 6 weeks that had had adrenal demeduilation at age 4 weeks and guanethidine injections over Weeks 2-4 after birth to produce peripheral sympathectomy (S rats), and in sham-sympathectomized sbamdemedullated control rats (SS rats). Plasma noreplnephrine and epinephrine levels were reduced by 94-96% in S rats. Arterial pressures were also reduced by 30% in S rats, which, nevertheless, had hearts and aortas of normal size respective to body weight. With aortic coarctation, femoral arterial pressures did not increase but carotid pressures rose by 18-25% (p < 0.01). Expressed in terms of body weight, heart weights increased 75% and 50% (p < 0.001) and weights of eh* thoracic portion of the aorta Increased 58% and 37% (p < 0.05) with coarctation in SS and S rats, respectively. In SS rats there was also a rise in weight (26%) of the normotensive abdominal portion of the aorta (p < 0.01); in contrast, this was not true in S rats. In both SS and S rats, wall water contents of thoracic aorta, abdominal aorta, and thoracic vena cava increased by 3-8% with coarctation (p < 0.02). The normal size of heart and aorta in S rats, despite lower arterial pressures, suggests that factors other than pressure and sympathoadrenergic stimuli influence cardiovascular growth in young rats. The increased weight of the abdominal aorta in coarcted SS rats suggests that vascular wall hypertrophy in hypertension does not require elevated intravascular pressures. Increases in heart and thoracic aortic weight with coarctation in S rats suggest that cardiovascular hypertrophy may occur in the virtual absence of sympathoadrenergic stimuli. However, in the absence of both pressure and catecholamine influences, vascular hypertrophy apparently does not occur. Finally, these studies provide evidence for vascular wall "waterlogging" in coarctation hypertension in rats not attributable to elevated levels of intravascular pressure and occurring despite the virtual absence of sympathoadrenergic influences. These findings support the hypothesis that humoral factors are involved in vascular wall "waterlogging" in hypertension. (Hypertension 1: 486-492, 1979) KEY WORDS • cardiovascular growth • guanethidioe • sympathectomy I N coarctation hypertension in rats, "waterwater and sodium content in normotensive vessels are logging" occurs in the walls of the normotenrises in wall potassium content, 1 suggesting the sive portion of the aorta downstream to the development of hypertrophy or hyperplasia of coarctation and also in veins.1 This finding strongly vascular smooth muscle. In the present experiments, suggests that neurogenic or humoral factors, or both, changes in weight and composition of cardiovascular must be involved in the pathogenesis of these comtissue with coarctation hypertension in rats were inpositional changes. Accompanying the increases in vestigated. In addition, the role of neurogenic influences in these abnormalities was evaluated in...

An Assessment of the Effectiveness of Neonatal Treatment With Guanethidine as a Means of Producing Sympathectomy

“…(1976), causes a profound reduction in cardiac noradrenaline content. The extent of depletion which we measured in the ventricles is within the range reported in the literature for whole hearts (Johnson et al, 1976;Grzanna & Coyle, 1978;Friedman et al, 1979;Overbeck, 1979;Levens et al, 1981). However, we also measured the noradrenaline content of separate right and left atria (which has not been previously done), and found some evidence for reinnervation in these tissues, since there was an increase in their noradrenaline content between 9 and 26 weeks after birth.…”

“…Thus, systolic and diastolic blood pressures measured in the conscious and anaesthetized states were not significantly different. Other workers have found that arterial blood pressure is significantly lower in rats treated with guanethidine either in the conscious state (Overbeck, 1979) or when anaesthetized with pentobarbitone (Simon, 1981). However, in both those studies the adrenal glands of the guanethidinetreated animals had been demedullated.…”

“…In all those studies, evaluation of the extent of the sympathectomy was based on the measurement of 0007-1188/82/080557-08 $01.00 tissue or plasma catecholamine levels (Grzanna & Coyle, 1978;Friedman, Tassinari, Heine & Iwai, 1979;Overbeck, 1979;Levens, Peach & Carey, 1981) or the pressor responsiveness of the anaesthetized rat to noradrenaline and tyramine (Friedman et al, 1979;Simon, 1981). However, there is some discrepancy in the literature regarding the degree of catecholamine depletion caused by the regime of guanethidine treatment outlined by Johnson et al (1976).…”

Structural and functional consequence of neonatal sympathectomy on the blood vessels of spontaneously hypertensive rats.

“…53 Our finding that cardiac hypertrophy in the SHR was unaffected by sympathectomy is consistent with previous findings in the SHR sympathectomized by anti-NGF, in which left ventricular hypertrophy was still present despite the prevention or amelioration of hypertension development. 17 " 19 Whether humoral factors are involved in causing cardiovascular hypertrophy in the SHR, as in the case of the coarctation model of hypertension, 55 is not known. In conclusion, our results suggest that the peripheral sympathetic nerves are involved in the development of hypertension in the SHR and that this involvement may be manifested through its trophic effect on the arteries in young SHR.…”

Limited maximal vasodilator capacity of forearm resistance vessels in normotensive young men with a familial predisposition to hypertension.

“…This suggests that the contribution of blood pressure elevation to structural vascular changes may be small. It is conceivable that hereditary predisposition might make vascular smooth muscle more susceptible to pressure loads (Folkow et al, 1958;Brody and Zimmerman, 1976) or neurohumoral stimuli (Bevan, 1975;Bevan and Tsuru, 1979;Hart et al, 1979;Overbeck, 1979) and produce abnormality in response to even a small increase of such stimuli.…”