Sympatho-adrenal mechanisms regulating cardiovascular hypertrophy in primary hypertension: a role for rilmenidine?
OBJECTIVE
Overactivity of the sympatho-adrenal system has long been considered a major factor contributing to blood pressure elevation in primary hypertension in humans and experimental animals. Our aim has been to elucidate its role in the development of cardiovascular hypertrophy in hypertensives.


METHODS
Two studies have been performed in spontaneously hypertensive rats (SHR). One involved irreversible inhibition of the sympatho-adrenal system in newborn SHR using a sympathectomy procedure combined with prolonged alpha1-adrenoceptor blockade. The other involved reversible, long-term inhibition of the sympatho-adrenal system in young but mature SHR, by treatment with rilmenidine, a centrally active antihypertensive agent interacting with imidazoline receptors. Their effects on cardiovascular structure were examined.


RESULTS
Sympathectomy plus alpha1-adrenoceptor blockade prevented the development of cardiac and vascular hypertrophy in adolescent SHR and these effects were maintained later in life. Rilmenidine administered to older (9-week) SHR also attenuated cardiac hypertrophy, abolished perivascular fibrosis associated with the intramyocardial vessels, and normalized vessel structure in the richly sympathetically innervated mesenteric vasculature. These effects were only partially related to the level of blood pressure reduction.


CONCLUSIONS
Inhibition of the sympatho-adrenal system not only reduces blood pressure to normotensive levels in SHR but also has beneficial effects on cardiovascular structure, potentially reducing risk factors for cardiac and renal abnormalities frequently seen in long-term hypertensives. Therapeutically, these effects are likely to be achieved with rilmenidine.
Bobik
A
A
Baker Medical Research Institute Melbourne, Victoria, Australia.
Dilley
R
R
Kanellakis
P
P
D000311:Adrenal Glands / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D006332:Cardiomegaly / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D006984:Hypertrophy / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology*; D000077769:Rilmenidine; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
D000959:Antihypertensive Agents; D010080:Oxazoles; D000077769:Rilmenidine; D009638:Norepinephrine