Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion

Area of Science:

• Cardiovascular Physiology
• Vascular Biology
• Cellular Communication

Background:

• Gap junctions, formed by connexins (Cx), are vital for intercellular communication in arterioles.
• Previous studies indicated connexin 40 (Cx40) deficiency impairs dilatory signal conduction.
• The role of Cx40 in hypertension and vascular resistance remains unclear.

Purpose of the Study:

• To investigate the presence and mechanisms of hypertension in Cx40-deficient mice.
• To determine if hypertension in Cx40(-/-) mice is a direct effect or due to secondary factors.
• To assess the impact of Cx40 deficiency on vascular reactivity and vasomotion.

Main Methods:

• Measurement of mean arterial pressure and heart rate in conscious Cx40-deficient (Cx40(-/-)) and wild-type mice.
• Pharmacological blockade of nitric oxide synthase and angiotensin AT(1)-receptor antagonism.
• Assessment of microcirculatory responses to acetylcholine and sodium nitroprusside.
• Observation of arteriolar vasomotion in vivo.

Main Results:

• Cx40(-/-) mice exhibited elevated mean arterial pressure (20-25 mmHg) compared to wild-type controls, without heart rate differences.
• Neither NO synthase inhibition nor angiotensin AT(1)-receptor blockade differentially affected blood pressure between genotypes.
• Endothelial-dependent and -independent vasodilation responses were similar in both groups.
• Cx40(-/-) arterioles displayed spontaneous, irregular vasomotion, including temporary vessel closure.

Conclusions:

• Loss of Cx40 is associated with hypertension in mice, independent of angiotensin II signaling.
• Altered efficacy of nitric oxide or other endothelial dilators does not explain the hypertension.
• Irregular arteriolar vasomotion in Cx40(-/-) mice suggests impaired peripheral vascular resistance regulation.