Methylprednisolone-induced hypertension. Role for the autonomic and renin angiotensin systems.
The role of the autonomic nervous system (ANS) in the pathogenesis of hypertension induced by methylprednisolone (20 mg/kg/week subcutaneously) was studied in rats before and during chronic renin angiotensin system (RAS) blockade with captopril (20 mg/kg/every 8 hrs by mouth). Sympathetic nervous system (SNS) blockade was accomplished by the intravenous (i.v.) administration of propranolol (0.20 mg/100g) plus phentolamine (1.25 mg/100g/i.v.) and ganglionic (G) blockade by the use of pentolinium tartarate (0.5 mg/100g/i.v.). After 4 weeks, methylprednisolone-treated animals showed significant decreases in mean arterial pressure (MAP) with both SNS (-34 +/- 2 mm Hg) and G (-56 +/- 3 mm Hg) blockades; during chronic RAS blockade, even greater falls in MAP were observed (SNS = -43 +/- 2 mm Hg and G = -75 +/- 3 mm Hg). Nevertheless, for both groups the levels of MAP obtained during SNS and G blockades were higher than those observed in their control groups. At the end of second week, however, in captopril-treated hypertensive rats the values of MAP obtained during ANS blockade were lower than those observed in the control group. An increased responsiveness to exogenous administration of norepinephrine (NE) was observed in animals receiving methylprednisolone and captopril. It is concluded that methylprednisolone hypertension in the rat may be initially explained by activation of RAS and ANS. At later phases, a third mechanism has to be postulated to explain the hypertensive state.
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology*; D008297:Male; D008775:Methylprednisolone; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects
D005730:Ganglionic Blockers; D002216:Captopril; D009638:Norepinephrine; D008775:Methylprednisolone