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120. **. *. 100. 80. Contraction (% of pH 7.4). 60. 100 nM ET-1. 10 mM verapamil. 40. pH 7.4. pH 6.8. 20. 0. - + - + Glibenclamide. 24.8 mM KCl. 300 nM PE. 300 nM PE. 100 nM ET-1. pH 7.4. pH 6.8.

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INTRODUCTION

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Introduction

120

**

*

100

80

Contraction (% of pH 7.4)

60

100 nM ET-1

10 mM verapamil

40

pH 7.4

pH 6.8

20

0

- + - + Glibenclamide

24.8 mM KCl

300 nM PE

300 nM PE

100 nM ET-1

pH 7.4

pH 6.8

Ca2+-free solution

24.8 mM KCl

pH 6.8

pH 7.4

n = 4-5

pH 7.4

pH 6.8

Fig. 5.Representative recording showing the effects of acidosis on the endothelin-1-induced contraction in Ca2+-free solution

Fig. 2.Representative recordings showing the effects of acidosis on the phenylephrine- and KCl-contracted human internal mammary artery

100 nM ET-1

pH 7.4

pH 6.8

100

**p < 0.01 versus control

##p < 0.01 versus KCl

Fig. 6.Representative recordings showing the effects of acidosis on the endothelin-1-induced contraction in Ca2+-containing solution

**

80

60

**##

Contraction (% of pH 7.4)

40

20

0

24.8 mM KCl

300 nM PE

Fig. 3.Quantification of the relaxant effects of acidosis on contractile responses to KCl and phenylephrine

Fig. 7. Representative recordings showing the effects of acidosis on the endothelin-1-induced contraction in in the presence of verapamil

+

K+

Ca2+

H+

Out

Hyperpolarisation

n = 5

-

VDCC

In

K+

0.5 g

+

H+

Ca2+

*p < 0.05; ** p < 0.01

versus control

2 min

↓[Ca2+]i

Relaxation

pH 6.8

64.8 mM KCl

Fig. 1.Representative recording showing the effect of acidosis on the resting tension of isolated human internal mammary artery

Fig. 4.Quantification of the relaxant effects of acidosis on contractile responses to KCl and phenylephrine in the presence of glibenclamide

Fig. 8.Scheme illustrating the events occurring under acidic conditions and resulting in relaxation of human internal mammary artery

ROLE OF ATP-SENSITIVE POTASSIUM CHANNELS IN ACIDOSIS-INDUCED RELAXATION OF HUMAN VESSELSDileep K. Rohra, Hasanat M. Sharif, Hina S. Zuberi, Kiran Sarfraz, Mohammad N. Ghayur, Anwarul H. Gilani,Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi

INTRODUCTION

  • The contractile state of vascular smooth muscle can be regulated by many factors including changes in pH.

  • Although the pH of blood and extracellular fluids is generally maintained at around 7.4, there are various pathophysiological conditions such as diabetes mellitus, renal dysfunction, and pulmonary edema, in which a significant decrease in pH occurs

AIM OF STUDY

  • The aim of the present study was to investigate the effects of acidosis on the contractility of human internal mammary artery

METHODOLOGY

  • The human left internal mammary artery (LIMA) was obtained from the Cardiothoracic Section of the Department of Surgery, The Aga Khan University Hospital. The arteries of patients, who underwent coronary artery bypass grafting operation, were used in the study.

  • The standard bypass operation involves using the LIMA as a bypass conduit. The artery is harvested in almost all operations and a portion of it is usually discarded after tailoring it to the appropriate length for the recipient artery. This normally discarded distal end of the human LIMA was used in the isometric tension recording experiments.

  • Informed Consent prior to surgery was obtained from all the patients whose LIMA was used for experiments.


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