Effects of antihypertensive therapy with angiotensin converting enzyme inhibitors or calcium antagonists on spontaneous cyclic vasomotor activity in small resistance arteries of spontaneously hypertensive rats.
OBJECTIVE
Spontaneous cyclic vasomotor activity can occur in small resistance arteries in vitro after precontraction with a vasoconstrictor. Calcium and potassium channels and nitric oxide synthesis or release seem to be involved in the genesis of this vasomotor activity. We therefore investigated the effects of chronic antihypertensive therapy with calcium antagonists and angiotensin converting enzyme (ACE) inhibitors on the amplitude and frequency of cyclic vasomotor activity in vitro in spontaneously hypertensive rats (SHR).


METHODS
SHR were treated with fosinopril at 25 mg/kg per day or lacidipine at 10 mg/kg per day or nitrendipine at 30 mg/kg per day, from the age of 4 to 12 weeks. Data were compared with those obtained in untreated SHR and Wistar-Kyoto (WKY) rats. Half the rats were killed at 13 weeks of age, and the remaining half were killed at 38 weeks of age. The mesenteric small resistance arteries were dissected, mounted on a micromyograph and then contracted submaximally with noradrenaline. Acetylcholine was then added to the organ bath.


RESULTS
More than 50% of the vessels showed cyclic vasomotor activity. The frequency and amplitude of this activity were greater in SHR than WKY rats after noradrenaline and after acetylcholine. At 13 weeks of age (but not at 38 weeks of age), treatment with a calcium antagonist (either lacidipine or nitrendipine) significantly reduced the frequency and amplitude of the vasomotor activity, probably by interfering with calcium entry. No change was observed after fosinopril.


CONCLUSIONS
Antihypertensive treatment with different drugs may affect cyclic vasomotor activity differently, probably by interfering with cellular mechanisms involved in its genesis. The effects of calcium antagonists on cyclic vasomotor activity are still present after short-term but not after long-term treatment withdrawal.
Rizzoni
D
D
Semeiotica e Metodologia Medica, University of Brescia, Italy.
Porteri
E
E
Castellano
M
M
Bettoni
G
G
Muiesan
M L
ML
Salvetti
M
M
Cinelli
A
A
Agabiti-Rosei
E
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers