Alpha adrenoceptors and autonomic mechanisms in perinephritis hypertension in the rabbit.

Abstract

SUMMARY Increased pressor responses to norepinephrine and other pressor agents have been reported to occur in human essential hypertension and in several animal models of experimental hypertension. These increased responses might be related to the development of hypertension or could be a secondary consequence of the elevation in blood pressure. We have examined pressor responses to alpha-adrenoceptor agonists and to angiotensin II in male New Zealand White rabbits with perinephritic hypertension. Increased pressor responses were observed for the a, adrenoceptor agonist phenylephrine and the mixed a r /a 2 -adrenoceptor agonist norepinephrine but not for the « 2 adrenoceptor selective agonist guanabenz or angiotensin II. The increase occurred within 7 days of surgery and in some animals was observed when mean arterial pressure was not significantly elevated. It could not readily be attributed to intimal thickening or hypertrophy of the arterial wall, altered basal levels of norepinephrine or epinephrine, changes in norepinephrine clearance, /3-adrenoceptor interactions, or decreased baroreceptor sensitivity. However, the possibility that vascular hypertrophy and decreased baroreflex sensitivity may contribute to the increase at later times cannot be excluded. In all tissues examined, specific prazosin binding was decreased in the older animals and specific clonidine binding was decreased in forebrain. However, these changes were observed In both hypertensive and sham-operated animals and were probably age-related. We believe the increased response to a,-adrenoceptor agonists may be related to changes at a postreceptor site in the coupling of receptor activation to smooth muscle contraction. 1 " 2 Similar observations have been made in animal models of experimental hypertension including spontaneously hypertensive rats 3 and renal hypertensive rabbits. 4 5 Changes in norepinephrine responsiveness may be mediated by /3-receptors, classical postsynaptic a,-adrenoceptors, the presynaptic regulatory a 2 -adrenoceptors, or the recently proposed postsynaptic aj-adrenoceptor 6 ' 7 which may participate in regulation of peripheral resistance. Increased responses to norepinephrine could also be the result of changes in the number of adrenoceptors or their affinity for the neurotransmitter or alternatively secondary to structural changes in the vessel wall. Changes in a-adrenoceptor number have been observed in several brain regions from spontaneously

Vascular amplifier properties in renovascular hypertension in conscious rabbits. Hindquarter responses to constrictor and dilator stimuli.

“…Moreover, since the properties of the arterial baroreceptors themselves are 130 HYPERTENSION VOL 9, No 2, FEBRUARY 1987 impaired in hypertension, 22 without the use of autonomic block any differences in the dose-response curve parameters between the hypertensive and normotensive rabbits will be confounded by the opposing • effects of the local vascular properties (which are enhanced in hypertension) and the arterial baroreceptor properties (which are impaired). We also suggest that change in MAP 7 is not necessarily an index of vascular responsiveness, since arterial pressure will depend on both vascular and cardiac factors, the latter complicating interpretation, especially during i.v. administration of drugs.…”

“…Our protocol differs in a number of respects from that of Hamilton and Reid,7 who used rabbits with intact reflexes and studied only changes in blood pressure. Our use of autonomically blocked rabbits prevented changes in vascular tone through various baroreceptor reflexes that are brought into play in the intact animal when the blood pressure changes during drug infusions.…”

“…By contrast, Folkow et al 3 studied the local properties of isolated, perfused vascular beds, and this was also largely the case in our experiments in conscious animals in which autonomic reflexes were eliminated. 4 ' 5 Another difference was that we studied the effects of drugs on vascular resistance in our earlier studies, 4 ' 5 whereas Hamilton and Reid 7 measured only blood pressure responses, which depend not only on resistance changes but also on cardiac factors.…”

“…One major difference in methodology was that in the experiments of Hamilton and Reid 7 and in most of those of Brody and colleagues 8 ' 9 autonomic function remained intact, so that the circulatory responses depended on the sum of local and reflex changes (see Discussion). By contrast, Folkow et al 3 studied the local properties of isolated, perfused vascular beds, and this was also largely the case in our experiments in conscious animals in which autonomic reflexes were eliminated.…”

Job Strain, Ethnicity, and Sympathetic Nervous System Activity

“…This drug mimics the short-term effects of stress on BP by increasing vasoconstriction. 13,17,18 Although studies consistently demonstrate that PE infusions lead to increased BP, the magnitude of this effect appears to be influenced by demographic factors, including hypertension status, age, gender, and ethnicity. 18,19 Ethnic and racial differences in pressor sensitivity to PE have been well-documented.…”