Effects of agmatine on the cardiovascular system of spontaneously hypertensive rats

The most interesting finding is the dose-dependent decrease in BP and HR with AGM, with much higher potency in anesthetized SHR than in pithed SHR. The discrepancy between BP responses to AGM in anesthetized and pithed SHR points to a central site of action of AGM. After central injection of AGM, cardiovascular responses are contrary to those after systemic administration. The increase in HR after AGM injection in the fourth ventricle is probably related to the nucleus tractus solitarius (NTS), because the administration of AGM icv was ineffective. By contrast, the increase in BP after icv AGM could be associated with projection fields of forebrain areas to the pressor centers within the RVLM. Previously it was shown that AGM administered intracisternally (ic) could induce an increase in BP. Furthermore, AGM (ic) increased sympathetic nerve activity and blocked arterial baroreflexes in anesthetized animals. Injected directly into the RVLM, AGM, unlike clonidine, is without any effect on BP or sympathetic nerve activity. The mode of action of AGM is generally not comparable to that of CLO which can: (1) decrease BP via centrally located I₁BS and α₂-adrenoceptors in the anesthetized rat and (2) increase BP dose dependently in pithed rats via peripheral α₂-adrenoceptors. Because AGM in much higher doses reduced BP in pithed SHR and because it did not modify the tension on isolated rat aortic rings as did CLO, effects on α₂-adrenoceptors are unlikely. Therefore, the biologic actions of AGM do not mimic those of classic CDS or imidazolines such as CLO. AGM, only via peripheral administration, can potentiate the CLO-induced hypotension and bradycardia in the anesthetized rat, because the administration into the fourth ventricle was ineffective in this experiment. We conclude that systemically administered AGM decreases sympathetic nerve activity and arterial blood pressure mainly by inhibition of sympathetic ganglionic transmission. Inversely, central administration of AGM displays a contrary role, because different injection sites elicited different HR and BP responses. Therefore, modulating activity of AGM within the central nervous system is possible, but the mechanism is currently unclear. Our data suggest that the postganglionic effects of AGM via α₂-adrenoceptors within the vasculature seem not to be involved, whereas preganglionic activity on IBS cannot be ruled out.