K V 1 channel‐mediated dilation to isoproterenol in cerebral arteries is disrupted in angiotensin II ‐induced hypertension

We previously reported the expression of scaffolding protein, postsynaptic density‐95 (PSD95) in rat cerebral vascular smooth muscle cells (cVSMC). PSD95 binds with K V 1 channels at the plasma membrane of cVSMC to mediate vasodilation. A membrane‐permeable peptide (K V 1‐C) that competes for PSD95 binding causes vasoconstriction and blunts vasodilation induced by isoproterenol (ISO). This study explores whether angiotensin II‐induced hypertension (AHT) alters ISO‐induced vasodilation and K V 1‐C peptide response. Sprague‐Dawley rats were infused by osmotic pumps with saline or angiotensin II (500ng/kg/min) for 14 days. Blood pressure was measured by tail‐cuff plethysmography. Cerebral arteries (CA) were isolated for pressure myography and protein lysate. Western blot analysis revealed K V 1.2 subunits were downregulated by ~70% (n=5) in CA lysates from AHT rats compared to saline rats. In pressurized CA, maximal vasodilation to ISO was reduced by half in AHT rats compared to saline rats. K V 1‐C peptide treatment had little effect on CA from AHT rats but it blunted ISO response in CA from saline rats to the level of AHT rats (n=5–8). These findings suggest that a loss of K V 1 channel expression and function in CA from AHT rats may account for the blunted ISO response and that K V 1‐C peptide confers similar disruption of PSD95‐mediated K V 1 channel function in CA from saline rats.