Microvascular effects of centrally acting antihypertensive drugs in spontaneously hypertensive rats.
We investigated the effects of oral long-term antihypertensive treatment using centrally acting sympathoinhibitory drugs on capillary density in the skin, skeletal muscle, and heart in the spontaneously hypertensive rat (SHR). Wistar Kyoto rats (WKY) were used as normotensive control groups. Functional capillary density was assessed using intravital fluorescence videomicroscopy and structural capillary density with histochemical analysis. Groups of 10 SHRs were orally treated over 28 days with clonidine (0.1 mg x kg x d), rilmenidine (1 mg x kg x d), or moxonidine (10 mg x kg x d). A group of WKY was also treated with clonidine (0.1 mg x kg x d). Treatment with all antihypertensive drugs induced a normalization of arterial pressure accompanied by a reversion of functional capillary rarefaction in the skeletal muscle and skin of SHR. Clonidine treatment also reduced arterial pressure and increased functional capillary density in the skin and skeletal muscle of WKY. Histochemical analysis showed that SHR had a lower capillary to fiber ratio in the skeletal muscle (P < 0.0001), which was normalized by all treatments. The capillary volume density to fiber volume density ratio in the left ventricle of SHR was also significantly reduced (P < 0.0001). However, myocardial capillary rarefaction was not altered by the different treatments. In conclusion, the results showed that long-term antihypertensive treatment with centrally acting drugs enhanced tissue perfusion and reversed capillary rarefaction in the skeletal muscle of SHRs.
Nascimento
Alessandro Rodrigues
AR
Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
Lessa
Marcos Adriano
MA
Sabino
Bruno
B
Bousquet
Pascal
P
Tibiriçá
Eduardo
E
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002196:Capillaries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003000:Clonidine / Q000494:pharmacology; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D018482:Muscle, Skeletal / Q000098:blood supply; D010080:Oxazoles / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000077769:Rilmenidine; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000959:Antihypertensive Agents; D007093:Imidazoles; D010080:Oxazoles; C043482:moxonidine; D003000:Clonidine; D000077769:Rilmenidine