Ramipril treatment alters Ca2+ and K+ channels in small mesenteric arteries from wistar-kyoto and spontaneously hypertensive rats

• Published in: American journal of hypertension 2002-10, Vol.15 (10), p.879-890
• Main Authors: Cox, Robert H., Lozinskaya, Irina, Matsuda, Kyoko, Dietz, Nancy J.
• Format: Article
• Language: English
• Subjects: angiotensin converting enzyme inhibitors; Antihypertensive agents; Biological and medical sciences; Cardiovascular system; force maintenance; Genetic hypertension; K+ channels; L-type Ca2+ channels; Medical sciences; membrane mechanisms; mesenteric arteries; Pharmacology. Drug treatments
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(02)02990-4

Numerous studies have emphasized the important role of altered Ca2+ channel function in hypertension. We previously showed that Ca2+ currents measured in myocytes isolated from both Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) small mesenteric arteries closely correlated with systolic blood pressure (BP) during normal development. The purpose of the present experiments was to determine whether antihypertensive therapy with an angiotensin converting enzyme inhibitor normalizes Ca2+ channel function in SHR myocytes along with BP. Ramipril (3.5 mg/kg/day) was added to the drinking water of 12-week-old male WKY and SHR for 8 weeks. Segments of small mesenteric arteries were used for isometric contraction studies, and for isolation of myocytes for measurement of Ca2+ and K+ currents (ICa and IK) by patch clamp methods. Ramipril treatment decreased systolic pressure in WKY and SHR, decreased heart weight and heart weight-to-body weight ratio in SHR, and decreased body weight in WKY. Maximum contractile responses to Bay k 8644 in SMA from ramipril-treated SHR were smaller compared to untreated SHR (10% ± 2% ν 55% ± 7% of the response to 120 mmol/L KCl). The smaller responses in WKY were not affected by ramipril treatment (11% ± 4% ν 8% ± 3%). Contractile responses to 10 mmol/L tetraethylammonium (TEA) were not different in untreated versus ramipril-treated SHR (65% ± 6% ν 82% ± 8%) but were increased in treated WKY (4% ± 1% ν 35% ± 9%). Ramipril treatment decreased peak ICa and equalized the voltage-dependence of ICa activation between SHR and WKY. The IK measured from holding potentials of −60 and −20 mV were significantly smaller in treated SHR and WKY compared to their untreated counterparts, as was the component of IK measured in the presence of 100 nmol/L iberiotoxin. These results show that ramipril treatment decreases arterial pressure and Ca2+ channel function in SHR as expected but unexpectedly also decreases IK in both WKY and SHR. These results suggest that angiotensin may have a BP independent effect on ion channel function in arterial smooth muscle.