The effects of anti-hypertensive therapy on the structural, mechanical and metabolic properties of the rat aorta.
The vascular system exhibits altered growth, calcium responses and metabolism during hypertension. To relate such changes, we compared histological, tension and metabolic responses in the aorta from 32-week-old spontaneously hypertensive rats (SHRs), normotensive Wistar-Kyoto (WKY) rats, and SHRs treated with Verapamil (V) and ACE-inhibitor, Trandolapril (T) as well as a combination of the two treatments (C). Vascular hypertrophy was apparent in the SHRs. Contractile responses induced by 50 mmol/1 KCl and 2.5 mmol/1 Ca2+ were significantly lower in the SHR (64.4 mN/mm2 vs. 49.2 mN/mm2), but an associated increase in Ca2+ -sensitivity (EC50 of extracellular Ca2+ (mumol/1): SHR, 456 vs. WKY, 616) normalised tension generating ability. All treatments led to significant decreases in blood pressure, although only T and C treated animals became normotensive with concomitant normalisation of vascular hypertrophy. An increase in oxygen consumption was apparent in the SHR aorta, which was associated with significant differences in the activities of key metabolic enzymes. Anti-hypertensive treatment normalised many of the metabolic parameters, with the C therapy being the most efficacious. We conclude that the treatment of hypertension by combined therapy leads to a better normalisation of structural, contractile, and metabolic parameters in the SHR, than either treatment alone and that metabolic changes with the pathology are resolved with appropriate therapy.
Clark
J F
JF
Department of Biochemistry, University of Oxford, UK. smooth@bioch.ox.ac.uk
Radda
G K
GK
Boehm
E A
EA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D014665:Vasodilator Agents; C052035:trandolapril; D014700:Verapamil