Neurogenic and Humoral Factors Controlling Vascular Resistance in the Spontaneously Hypertensive Rat

Abstract

The mechanism of sustained hypertension in spontaneously hypertensive rats has not been elucidated. In the present investigation, vasoconstrictor responses to a variety of neurogenic and humoral interventions were studied in the perfused hindquarters of Okamoto spontaneously hypertensive rats and normotensive Wistar rats. In addition, central sympathetic electrical discharge was measured. Vasoconstrictor responses in the hindquarters to lumbar sympathetic nerve stimulation were unchanged or reduced in the spontaneously hypertensive rats, but the responses to intra-arterially administered norepinephrine and epinephrine were enhanced. Vascular responses to intra-arterially administered tyramine, angiotensin, and barium chloride were also greater in the spontaneously hypertensive rats. Vascular resistance was significantly higher in the spontaneously hypertensive rats, and this difference remained following bilateral lumbar sympathectomy. Despite elevated systemic blood pressure, integrated nerve activity at rest was not different in the spontaneously hypertensive rats. The inverse relationship between arterial blood pressure and sympathetic nerve discharge was not different between spontaneously hypertensive and control rats when pressure was either raised or lowered. Changes in efferent sympathetic discharge produced by activation of chemoreceptors (asphyxia) were somewhat less in the spontaneously hypertensive rats. The contribution of low-pressure baroreceptors (45° tilt) to activation of sympathetic vasomotor tone was not different in the spontaneously hypertensive rats despite a greater decline in systemic blood pressure during the procedure. These data demonstrate that established hypertension in the spontaneously hypertensive rat does not derive from either enhanced central adrenergic discharge or altered central integration of afferent information from peripheral sensory receptors but may result from humoral (e.g., increased reactivity to vasoconstrictors) or structural factors. KEY WORDSvascular reactivity adrenergic vasomotor tone catecholamines central vasomotor control baroreceptors sympathetic nervous system chemoreceptors sympathectomy• The spontaneously hypertensive rat was isolated as a pure inbred strain by Okamoto and Aoki (1). In these rats, the hypertensive state develops without provocation and is readily apparent soon after weaning age (2). The pathophysiology underlying the development and the maintenance of hypertension in the spontaneously hypertensive rat has not been elucidated. Of the many factors that could contribute to the maintenance of hypertensive state, only the renin-angiotensin pressor system seems to be excluded from participation (3, 4). Some investigators (5-7) have suggested that the hypertensive state is maintained by an increase in neurogenic vasoconstrictor influences which should theoretically be associated with 764an increase in the turnover of catecholamines (8). However, a growing body of reports indicates a decrease in catecholamine turnover in peripheral t...

Contribution of the sympathetic nervous system to vascular resistance in conscious young and adult spontaneously hypertensive rats.

“…The results of the present study do not confirm previous reports, several of which are from this laboratory, of increased vascular reactivity to pressor agents in isolated perfused kidneys and hindquarters. 28 ' " " It may well be that factors such as anesthesia, perfusion pumps,, and artificial perfusion media have a more profound effect on vascular reactivity than has been appreciated. It is also possible that increased vascular reactivity to norepinephrine might be present in conscious SHR prior to 8 weeks of age.…”

Abnormal vascular phosphoinositide hydrolysis in the spontaneously hypertensive rat

“…The responses to neurotransmitters have been extensively studied but the overall picture is unclear. Results of experiments using intact animals or vascular beds suggest that noradrenaline sensitivity is greater in spontaneously hypertensive rats (SHR) than in Wistar Kyoto (WKY) controls (Lais et al, 1974;Berecek et al, 1980). Experiments using isolated preparations suggest that it is only part of the SH vasculature which shows increased sensitivity.…”

Ratos Espontaneamente Hipertensos E Neuropatias Periféricas

“…Independentemente da controvérsia quanto à similaridade, ou não, entre o SHR e a hipertensão essencial do homem, este modelo tem se revelado bastante útil para melhor compreensão de mecanismos fisiopatológicos, quer do pró-prio modelo em si, quer da hipertensão essencial do homem. Embora a hipertensão dos SHR seja de desenvolvimento espontâneo, fatores ambientais tais como, ingestão exagerada de sódio 11 , estresse 12 , alterações sociais 13 , e alterações do ciclo claro/escuro 14 afetam esse desenvolvimento.…”